Login to MyKarger

New to MyKarger? Click here to sign up.



Login with Facebook

Forgot your password?

Authors, Editors, Reviewers

For Manuscript Submission, Check or Review Login please go to Submission Websites List.

Submission Websites List

Institutional Login
(Shibboleth or Open Athens)

For the academic login, please select your country in the dropdown list. You will be redirected to verify your credentials.

Original Research Article

Open Access Gateway

The First Report of a Patient with Probable Variant Creutzfeldt-Jakob Disease in Turkey

Adapınar D.Ö.a · Saylısoy S.b · Yenilmez Ç.c · Aslan H.d · Ertan B.a · Artan S.d · Güleç G.c · Susuz Ç.a · Adapınar B.b

Author affiliations

Departments of aNeurology, bRadiology, cPsychiatry and dMedical Genetics, Eskisehir Osmangazi University Medical Faculty, Eskisehir, Turkey

Corresponding Author

Demet Özbabalık Adapınar

Eskisehir Osmangazi University

TR–26480 Meselik/Eskisehir (Turkey)

E-Mail demetg@ogu.edu.tr

Related Articles for ""

Dement Geriatr Cogn Disord Extra 2011;1:429–432

Abstract

Variant Creutzfeldt-Jakob disease (vCJD) was first reported in the UK in 1996. Here, we report the first Turkish case of vCJD. A 47-year-old man, who has never lived outside of Turkey and had had no transfusion, was admitted to the University Hospital with speech disorder, cognitive decline and ataxia following depression, irritability, and personality change. The immunoassay of the 14-3-3 protein in the cerebrospinal fluid was negative. Brain magnetic resonance imaging revealed high-signal lesions involving the bilateral caudate and lentiform nucleus on T2- and diffusion-weighted imaging. The patient developed akinetic mutism 10 months after disease onset. The clinical presentation and neuroimaging findings were compatible with the vCJD cases reported since 1996 and met the World Health Organization’s case definition for probable vCJD.

© 2011 S. Karger AG, Basel


Introduction

Creutzfeldt-Jakob disease (CJD), which is characterized by progressive dementia with a fatal and incurable course, is the most common human prion disease. There are 4 types of this disease: the sporadic (85%), familial (10–15%), iatrogenic (1%), and variant types [1]. Variant Creutzfeldt-Jakob disease (vCJD) was first reported in 1996 in the United Kingdom and has been causally linked to the consumption of cattle products contaminated with the bovine spongiform encephalopathy (BSE) agent [2]. To date, more than 215 cases of vCJD have been identified worldwide, including in the UK, France, Ireland, Italy, the USA, Canada, Saudi Arabia, Japan, The Netherlands, Portugal, Spain, and Taiwan. In the present paper, we report the clinical and radiological data of the first Turkish case of vCJD.

Case Report

A 47-year-old man, who was previously healthy and had no history of psychiatric or neurological disorders before the onset of this disease, presented with a 6-month history of progressive behavioral and personality changes, depression, and cognitive decline. His relatives reported that personality changes were his first symptoms. He had been a rigorous, disciplined, and frugal person, who was dependable at work and a valued member of his family; however, he became aggressive, extravagant, foul-mouthed, sexually disinhibited, and angry. His wife reported that the patient would have sudden outbursts of agitation, and 2 months later, these outbursts were followed by paranoid behaviors and possessiveness. Due to the psychiatric nature of his complaints, he was admitted to a psychiatry clinic, where he was diagnosed as having a manic disorder and was given atypical antipsychotic drugs. Three months later, the patient exhibited gait changes, ataxia and dysarthria, severe forgetfulness, difficulties in swallowing and eating, and incontinence. The patient developed involuntary movements in both of his feet, with dystonic aversion-inversion posturing and occasional erratic movements. He became dependent and apathetic and exhibited regressive behaviors. The patient also exhibited visual hallucinations, during which he reported seeing animals. Some of these complaints may have been side effects from his medication and, consequently, several of the patient’s medications were stopped or changed.

As a result of the progressive deterioration of the patient’s general status, his relatives transferred him to the Psychiatry Department of our University Hospital. After the neurological examination conducted at the Psychiatry Clinic, he was diagnosed as having rapid progressive dementia with early onset and was hospitalized at the Neurology Clinic. As reported in the patient’s medical history, he had never been exposed to cadaveric pituitary hormones, had never undergone a neurosurgical procedure, organ or tissue grafts, or a blood transfusion, and had never travelled to the UK or to any country with reported incidences of BSE.

The neurological examination revealed that the patient was disorientated in place and time. In addition, he was mute. Nystagmus and conjugate gaze dysfunction were present, as were cerebellar ataxia, dysmetria, and dysdiadochokinesia. The patient’s tone was slightly increased in his lower limbs, and his plantar responses were extensor.

The level of protein in his cerebrospinal fluid was increased, and no 14-3-3 protein was detected. An electroencephalogram showed a generalized slowing of wave, which was more evident in the left hemisphere, but did not have any periodic complexes. He was referred to the Radiology Department for cerebral MRI. On T2-weighted images and fluid-attenuated inversion recovery (FLAIR) images, hyperintense signal changes in the bilateral caudate nuclei (white arrows) and the lentiform nucleus (black arrows) were seen. In addition, hyperintensity in the bilateral thalamic region was less prominent than in the previously described areas (fig. 1a–c). Cortical hyperintensity was noted on diffusion-weighted imaging.

Fig. 1

MRI shows hyperintensity in the bilateral caudate (white arrows) and bilateral lentiform nucleus (black arrows) as well as in the bilateral thalamus (curved arrow) on axial T2-weighted image (a) and coronal FLAIR image (b). Ribbon-shaped hyperintense signals in the right central sulcus and bilateral parietal cortex at the convexity is seen on diffusion-weighted imaging (arrows) (b = 1,000 s/mm2) (c).

http://www.karger.com/WebMaterial/ShowPic/227504

Genotyping of the prion protein gene (PRNP) identified a P102L mutation and heterozygosity for methionine at codon 129.

The patient did not want to undergo a brain biopsy, and we continued to follow his progress at his home. At the time this report was written, the patient was alive, mute, and on bed rest.

Discussion

The patient described in the present report was the first probable case of vCJD in Turkey. The clinical features of this patient are consistent with the vCJD cases that have been identified in the UK and France, including psychiatric manifestations at the disease onset, a delayed occurrence of neurological signs, ataxia, and dementia [3]. In addition to the pulvinar sign that was present on the MRI and EEG, the patient fulfilled the WHO case definition for probable vCJD, the specificity of which is 100% [4]. Of note, a tonsil biopsy is not necessary if the clinical features and the MRI findings are compatible with vCJD, as the pulvinar sign is highly characteristic [5].

Sequencing analysis revealed that the patient had two different nucleotide changes in the coding region of the PRNP gene. The first one is the M129V polymorphism, and our patient was heterozygous for this alteration. Interestingly, all the patients who have undergone genotyping up to now have been homozygous for methionine at codon 129. This polymorphism is associated with susceptibility to prion diseases [6]. The second one is the P102L mutation, which was first identified in affected members of two unrelated families with Gerstmann-Sträussler disease. P102L is one of the most common PRNP mutations and also related to CJD.

This case highlights the difficulties in achieving an early diagnosis of vCJD. At the initial presentation, a variety of diagnoses were proposed, but vCJD was not considered in this patient. Instead, he was diagnosed as having an affective disorder at the psychiatry clinic. The delayed neurological signs in this patient pointed to the possibility of progressive dementia, which is not surprising given the frequency of psychiatric features that are observed by primary care physicians. These clinical features are often misleading. Almost half of the cases of vCJD were reviewed by a psychiatrist prior to the patients’ neurological referral [7]. A neurological etiology was usually suspected promptly after the patients developed objective neurological features, which resulted in a neurological referral in all of the cases. The single most important determinant of early diagnosis was the presence of objective neurological features. For this reason, all physicians must be careful when diagnosing rapidly progressing dementia that begins at a young age.

The results presented in this report indicate that patients with vCJD are still seen in the medical community. In the present study, we have reported the first Turkish vCJD case, which appeared 15 years after the first case in the UK.


References

  1. Johnson RT: Prion diseases. Lancet Neurol 2005;4:635–642.
  2. Will RG, Ironside JW, Zeidler M, Cousens SN, Estibeiro K, Alperovitch A, Poser S, Pocchiari M, Hofman A, Smith PG: A new variant of Creutzfeldt-Jakob disease in the UK. Lancet 1996;347:92.
  3. Brandel JP, Heath CA, Head MW, Levavasseur E, Knight R, Laplanche JL, Langeveld JP, Ironside JW, Hauw JJ, Mackenzie J, Alpérovitch A, Will RG, Haïk S: Variant CJD in France and the United Kingdom: evidence for the same agent strain. Ann Neurol 2009;65:233–235.
  4. World Health Organization: The revision of the surveillance case definition for variant Creutzfeldt-Jakob disease (vCJD). WHO/CDS/CSR/EPH/2001.5, 2002. Report of a WHO consultation.
  5. Collie DA, Summers DM, Sellar RJ, Ironside JW, Cooper S, Zeidler M, Knight R, Will RG: Diagnosing variant Creutzfeldt-Jakob disease with the pulvinar sign: MR imaging findings in 86 neuropathologically confirmed cases. Am J Neuroradiol 2003;24:1560–1569.
  6. Lukic A, Beck J, Joiner S, Fearnley J, Sturman S, Brandner S, Wadsworth JD, Collinge J, Mead S: Heterozygosity at polymorphic codon 219 in variant Creutzfeldt-Jakob disease. Arch Neurol 2010;67:1021–1023.
  7. Lépine J, Gastpar M, Mendlwicz J, Tylee A: Depression in the community: the first pan-European study DEPRES (Depression Research in European Society. Int Clin Psychopharmacol 1997;12:19–29.

Author Contacts

Demet Özbabalık Adapınar

Eskisehir Osmangazi University

TR–26480 Meselik/Eskisehir (Turkey)

E-Mail demetg@ogu.edu.tr


Article / Publication Details

First-Page Preview
Abstract of Original Research Article

Published online: December 24, 2011
Issue release date: January – December

Number of Print Pages: 4
Number of Figures: 1
Number of Tables: 0


eISSN: 1664-5464 (Online)

For additional information: https://www.karger.com/DEE


Open Access License / Drug Dosage / Disclaimer

Open Access License: This is an Open Access article licensed under the terms of the Creative Commons Attribution-NonCommercial 3.0 Unported license (CC BY-NC) (www.karger.com/OA-license), applicable to the online version of the article only. Distribution permitted for non-commercial purposes only.
Drug Dosage: The authors and the publisher have exerted every effort to ensure that drug selection and dosage set forth in this text are in accord with current recommendations and practice at the time of publication. However, in view of ongoing research, changes in government regulations, and the constant flow of information relating to drug therapy and drug reactions, the reader is urged to check the package insert for each drug for any changes in indications and dosage and for added warnings and precautions. This is particularly important when the recommended agent is a new and/or infrequently employed drug.
Disclaimer: The statements, opinions and data contained in this publication are solely those of the individual authors and contributors and not of the publishers and the editor(s). The appearance of advertisements or/and product references in the publication is not a warranty, endorsement, or approval of the products or services advertised or of their effectiveness, quality or safety. The publisher and the editor(s) disclaim responsibility for any injury to persons or property resulting from any ideas, methods, instructions or products referred to in the content or advertisements.

References

  1. Johnson RT: Prion diseases. Lancet Neurol 2005;4:635–642.
  2. Will RG, Ironside JW, Zeidler M, Cousens SN, Estibeiro K, Alperovitch A, Poser S, Pocchiari M, Hofman A, Smith PG: A new variant of Creutzfeldt-Jakob disease in the UK. Lancet 1996;347:92.
  3. Brandel JP, Heath CA, Head MW, Levavasseur E, Knight R, Laplanche JL, Langeveld JP, Ironside JW, Hauw JJ, Mackenzie J, Alpérovitch A, Will RG, Haïk S: Variant CJD in France and the United Kingdom: evidence for the same agent strain. Ann Neurol 2009;65:233–235.
  4. World Health Organization: The revision of the surveillance case definition for variant Creutzfeldt-Jakob disease (vCJD). WHO/CDS/CSR/EPH/2001.5, 2002. Report of a WHO consultation.
  5. Collie DA, Summers DM, Sellar RJ, Ironside JW, Cooper S, Zeidler M, Knight R, Will RG: Diagnosing variant Creutzfeldt-Jakob disease with the pulvinar sign: MR imaging findings in 86 neuropathologically confirmed cases. Am J Neuroradiol 2003;24:1560–1569.
  6. Lukic A, Beck J, Joiner S, Fearnley J, Sturman S, Brandner S, Wadsworth JD, Collinge J, Mead S: Heterozygosity at polymorphic codon 219 in variant Creutzfeldt-Jakob disease. Arch Neurol 2010;67:1021–1023.
  7. Lépine J, Gastpar M, Mendlwicz J, Tylee A: Depression in the community: the first pan-European study DEPRES (Depression Research in European Society. Int Clin Psychopharmacol 1997;12:19–29.
ppt logo Download Images (.pptx)


Figures
Thumbnail

Tables