The first case of variant Creutzfeldt-Jakob disease in the Netherlands
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- Sánchez-Juan, P., Houben, M.P.W.A., Hoff, J.I. et al. J Neurol (2007) 254: 958. doi:10.1007/s00415-006-0360-3
Sirs: In 1996, a new variant of Creutzfeldt-Jakob disease (vCJD) linked to the cattle bovine spongiform encephalopathy (BSE) epidemic was described in the United Kingdom (UK) [8, 2]. Up until now, 191 cases have been reported worldwide. Most of these cases have occurred in the UK (159), but in recent years vCJD has been identified in a number European countries with indigenous outbreaks of BSE, including 18 cases in France, four in Ireland, two in the Netherlands and single cases in Portugal, Italy and Spain. However, a growing number of cases of vCJD have also been identified in countries outside Europe including Japan (n = 1), the United States (n = 2) and Canada (n = 1) and also in Saudi Arabia (n = 1), in which BSE has not been identified. A number of the non-UK cases, including two Irish, the Canadian, the two US cases, and possibly the Japanese case, may well have been infected during periods of residence in the UK, but the majority of cases (n = 25) occurring outside the UK, like the two cases that developed in the Netherlands, had never visited the UK . In this study we describe the first patient identified with vCJD in the Netherlands .
The patient was a 26-year-old woman with previous medical history of two abortions in 1996 and in 1998 and a psychiatric history of anxiety and a phobic disorder since 1999. However, one year previous to the vCJD disease onset, she had completely recovered from her psychiatric problems and was able to function normally. She worked in a catering and food-processing business for 6 years, from 1998 to the disease onset. She consumed all types of meat frequently, including raw meat, and particularly processed meat products. She had no history of neurosurgical procedures, hormonal treatments, or tissue or organ grafts, and she had never received or donated blood. She never traveled to the UK. She had no family history of dementia or any other neurodegenerative disorder.
From November 2003, the patient developed new psychiatric symptoms, particularly anxiety and aggressive behavior. In spring 2004, the family also noticed some forgetfulness. A few months later, the psychiatric symptoms worsened. She suffered from panic attacks, became very dependent and apathetic, and showed regressive behavior. She also had visual hallucinations in which she saw animals. In July 2004, two weeks after a dental extraction, she started complaining of severe facial pain in her upper jaw. Her dentist examined her but no organic cause was found. At that point she was seen by a psychiatrist who suspected that she was suffering from anxiety and a conversion disorder.
In September 2004, the patient developed involuntary movements of her right foot, with dystonic eversion-inversion posturing and occasionally some jerking movements. She also developed paresthesiae in the lower limbs and gait difficulties, especially when walking in the dark. In November, the family also noticed dysarthria and problems in the motor coordination of the upper limbs. She had several episodes of blurring of vision. During this period, she was twice hospitalized in a psychiatric ward because of increasing anxiety, regressive behavior and facial pain.
From January to March 2005 the involuntary movements worsened significantly, accompanied by generalized stiffness, now involving all extremities. In March the patient was again hospitalized in a psychiatric ward with the clinical diagnosis of a conversion disorder, and treatment with Haloperidol was started. Two days later she suffered a tonic-clonic seizure followed by hyperthermia that required admission to an intensive care department. No cause was found for the persistent high temperature, and the neuroleptic medication was withdrawn. The patient was treated for malignant neuroleptic syndrome without success. The neurological state of the patient worsened rapidly.
Non-UK cases of vCJD may potentially have been infected during a period of residence in the UK in the 1980s and early 1990s (for example the US and Canadian cases). Our patient had never traveled to the UK, but may have been exposed through either indigenous BSE infected animals or BSE infected exports from the UK to the Netherlands during the 1980s and early 1990s. Thus far, all non-UK cases of vCJD who had never previously visited the UK show disease characteristics analogous to the UK cases. The clinical features, PRNP codon 129 genotype, neuropathological findings and western blot PrPSc isoform of our patient are indistinguishable from the United Kingdom vCJD cases, pointing towards a common etiological agent.
The Netherlands CJD surveillance system is part the EUROCJD group, a EU-funded network established in 1993 with the aim of monitoring the disease incidence and detecting new vCJD cases . In the Netherlands, only 80 BSE cases have been reported . The first case of variant CJD diagnosed in the Netherlands highlights the importance of continuing multinational surveillance of human prion diseases, even in countries with a low BSE incidence, during the preparation of this manuscript a second probable vCJD case has been ascertained in our country .
The early detection of vCJD patients is crucial as there are major public health implications, including of tracing of blood products from patients who were blood donors and tracing of surgical instruments, in this case dental instruments. Despite of a long disease course (18 months) the diagnosis in this patient was particularly difficult owing to the past psychiatric history. The brain MRI findings played a crucial role in the diagnosis by the treating neurologist (J.I.H.). This triggered the notification to the CJD registry in Rotterdam.
This case report underscores the value of the MRI in the diagnosis of vCJD and the need for an increased awareness of radiologists and neurologists of the MRI findings in vCJD, including in countries with a low incidence of BSE.
We are grateful to the relatives of the patient for their kind collaboration in collecting the clinical data. We thank Mark Head for performing the western blot analysis and providing figure 3. We thank Matthew Bishop and Alejandro Arias for performing the genetic analysis. We thank Prof. Berciano for his help in the edition of the figures. The national CJD surveillance is supported in the Netherlands by the Dutch Ministry of Health Welfare and Sports. Pascual Sanchez-Juan was supported by the postMIR grant Wenceslao Lopez Albo from the IFIMAV Institute of the Fundación Pública Marqués de Valdecilla.