Serial EEG findings in sporadic and iatrogenic Creutzfeldt–Jakob disease
Introduction
Transmissible spongiform encephalopathies or prion diseases are a group of diseases occurring both in humans and a wide variety of animals. Although the true nature of the agent causing transmissible spongiform encephalopathies has yet to be determined, a wealth of evidence indicates that an essential component of the infectious agent, termed prion, is composed of an abnormal isoform of the host encoded prion protein (PrPC), designated PrPSc (Glatzel et al., 2003).
Human prion diseases are categorized into sporadically occurring diseases (sporadic Creutzfeldt–Jakob disease, sCJD) or inherited forms (genetic Creutzfeldt–Jakob disease, fCJD). Alternatively these diseases may be caused by accidental transmission of prion-contaminated material, be it in the framework of neurosurgical interventions, or be it through injection of prion-contaminated hormones (iatrogenic Creutzfeldt–Jakob disease, iCJD). Variant Creutzfeldt–Jakob disease (vCJD), a new member of the family of acquired human prion diseases, is probably caused by uptake of material contaminated with bovine spongiform encephalopathy prions (Ironside et al., 2002, Ironside, 2003, Ironside et al., 2002).
Definite diagnosis of most human prion diseases is only possible by neuropathological examination of cerebral tissue originating from a brain biopsy or post-mortem examination. The diagnosis of a probable human prion disease, however, is based on clinical findings in combination with auxiliary examinations such as magnetic resonance tomography, cerebrospinal fluid (CSF) analysis and EEG findings.
The EEG still constitutes one of the most important investigations in the diagnosis of human prion diseases or in the judgment of the clinical course of this disease entity.
Surprisingly little is known on the temporal or spatial development of EEG patterns both in sCJD or iCJD. In this study we investigated the development of EEG patterns in a group of sCJD patients and iCJD patients with serial EEG recordings (minimum 4, maximum 29, mean 9.3), documented prior to prion exposure (iCJD) or during various disease phases (iCJD and sCJD). Iatrogenic CJD patients had been exposed to intracerebrally implantated, prion contaminated stereo EEG electrodes.
By examining 56 EEG patterns in 4 patients with sCJD and two patients with iCJD, we were able to substantiate the observation that frontal intermittent rhythmical delta activity (FIRDA) might represent an EEG pattern associated with the initial phase of clinical CJD, whereas typical periodic sharp wave complexes (PSWC) can only be observed at late stages of the disease, usually occurring with or shortly after the onset of myoclonus and akinetic mutism (Sun et al., 2003). EEG analyses in two patients with iCJD demonstrate that pathological EEG findings spread from the site of infection to other parts of the central nervous system suggesting a centrifugal spread of the agent causing human prion diseases.
Section snippets
Diagnosis of sporadic and iatrogenic CJD
Sporadic and iatrogenic CJD were diagnosed according to the classification criteria established by the WHO (Asher et al., 1999). For sCJD, definite sCJD can only be diagnosed via neuropathological examination. Probable sCJD encompasses rapid progressive dementia in less then 2 years and at least 2 out of 4 of the following clinical signs: myoclonus, cerebellar and/or visual symptoms, extrapyramidal and/or pyramidal signs and akinetic mutism. Additional investigations such as CJD-typical EEG
Patients characteristics for sporadic CJD
Patient 1. This patient, a 73 year old woman, with a disease duration of around 3 months, developed typical clinical signs of sporadic CJD with rapid progressive dementia followed by severe ataxia and myoclonic jerks (Table 1). She was tested positive for 14-3-3 in CSF and serial EEG analysis demonstrated CJD typical PSWC; documented 53–3 days before death (Fig. 1). Neuropathological, biochemical and genetic examination gave evidence of sCJD, MM1 (Parchi et al., 1999).
Patient 2. This patient, a
Discussion
The diagnosis of human prion diseases is based on the appraisal of clinical signs and symptoms and a number of auxiliary examinations. Over the last decades electroencephalography has been the method of choice in order to substantiate the diagnosis of a human prion disease. In the last years additional methods such as the elevation of markers of neuronal injury in the CSF have facilitated clinical diagnosis of human prion diseases and the combination of EEG and CSF analysis carries a positive
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