Table of contents
Material and Methods
Magnetic resonance imaging for initial diagnosis of sporadic Creutzfeldt Jakob disease
Sporadic Creutzfeldt–Jakob disease (sCJD) is a fatal neurodegenerative disorder caused by expression of abnormal human prion proteins in the brain. sCJD causes rapidly progressive dementia (RPD). For a definitive diagnosis, brain biopsy or autopsy is required (definite CJD). Premortally diagnosed patients are called probable CJD according to the diagnostic criteria of Zerr et al.
The aim of this case series is to show the reliability of magnetic resonance imaging (MRI) in the initial diagnosis of this disease compared to other diagnostic modalities. Furthermore we give a review of literature to confirm our observations.
Our case series consisted of six patients; four were diagnosed with definite sCJD and two with probable sCJD.
Diffusion weighted imaging (DWI), EEG and cerebrospinal fluid (CSF) was examined in all patients.
All patients showed diffusion restriction in the basal ganglia and/or cortex in DWI and CSF analysis was positive for 14-3-3 protein in five patients. EEG showed typical changes in three cases. The clinical examination revealed heterogenic results. One patient had typical MRI changes even present before the onset of symptoms.
Our case series and a literature review showed that DWI with ADC map are a highly sensitive and specific tools for the initial diagnosis of sCJD especially when clinical features appear atypical for the disease.
CJD is a very rare entity with an incidence of one in two millions. It is an infectious disease caused by abnormal proteins, which are called prions (1).
The so called prion hypothesis describes a transformation from the normal cellular prion protein into the pathologic form called scrapie, which tends to accumulate and induces neuronal cell death and spongiform changes of the brain (1).
Four different forms of CJD are known: the sporadic type (sCJD), the genetic type, the iatrogenic type and the variant type. Prion diseases have a fatal prognosis and no treatment exists (2).
We focused here on the most common form of prion disease: sCJD. Most patients with sCJD are about 60 – 70 years old. They typically present with RPD and focal neurologic signs including ataxia, pyramidal and extrapyramidal disorders or visual disturbances (2). The mean duration of the disease is 6 months with a range from several weeks up to two years (3).
Electroencephalogram (EEG) and the analysis of cerebrospinal fluid (CSF) may be helpful in the diagnosis. EEG shows periodic sharp wave complexes (PSWC) in about two thirds of sCJD patients (4).
The 14-3-3 protein is a neuronal protein which is released into the CSF as a result of extensive destruction of the brain tissue and therefore, this protein is also an important parameter for the detection of sCJD (5).
MRI has been proven to be a very powerful tool in the premortal diagnosis of CJD (6).
However the main problem is that a definite diagnosis can only be made by the autopsy report. According to the updated diagnostic criteria by Zerr et al (7), premortal probable sCJD is determined when two of the following four clinical features are met: 1. dementia, 2. visual or cerebellar signs, 3. pyramidal or extrapyramidal signs, 4. acinetic mutism. Additionally at least one of the following laboratory tests must be positive: 1. typical EEG (periodic sharp wave complexes), 2. detection of 14-3-3 protein in CSF in patients that suffer from sCJD for less than two years; and 3. MRI signal abnormalities in DWI or fluid attenuated inversion recovery (FLAIR)
The aim of this case series is to show the reliability of MRI in the initial diagnosis of CJD. The exact and early diagnosis is essential to exclude other treatable diseases.
Materials and Methods:
The institutional review board approved this HIPPA compliant retrospective study; patient informed consent was waived.
A database search including the term Creutzfeldt Jakob disease revealed the names of twelve patients during the last ten years. We had to exclude five patients due to the lack of MRI data. Another patient was excluded because of genetic CJD. All patients had a negative history of familial diseases or exposure to known prion-contaminated, neurosurgical instruments, tissue grafts, and pituitary extracted hormones.
This case series consists of six patients, four females and two male. Four patients were diagnosed with definite sCJD and two with probable sCJD according to the updated diagnostic criteria.
DWI was available in all of them. Furthermore all patients received EEG and CSF examination for 14-3-3 protein. Imaging Characteristics:
We performed MRI examinations with a 1.5 Tesla system (Siemens Magnetom Espree). The imaging protocol included a DW single-shot spin echo echoplanar sequence acquired in the anterior commissure-posterior commissure (diffusion gradient b values of 0 and 1000 s/mm², repetition time [TR] 5000 ms, echo time [TE] 114 ms, slice thickness 6 mm with no gap, matrix of 192x100 pixels, and field of view of 230 mm); fluid-attenuated inversion recovery (FLAIR; TR/TE 9770/99 ms, inversion time 2200 ms); and T2-weighted turbo spin echo sequences (TR/TE 4500/85 ms). For diffusion weighted MRI, the diffusion gradients were successively and separately applied in 3 orthogonal directions for a total acquisition time of 97 seconds. Trace images were then generated and ADC maps were calculated with dedicated software tool (Syngo; Siemens).
Data Acquisition: MRI scans were interpreted by an experienced neuroradiologist. We reviewed the medical history for clinical examination, CSF analysis and EEG. Furthermore we compared our findings with a review of literature.
A 70-year-old female patient was transferred to hospital because of vertigo. The first symptoms appeared three weeks ago. The initial clinical examination revealed ataxia. The patient was initially orientated and no cognitive impairment was detectable. MRI revealed restricted diffusion in the cortex of the occipital, frontal and temporal lobe on the left side and the left sided caudate nucleus (Fig. 1). No changes have been detected on FLAIR and T2w sequences. EEG showed PSWC on the left hemisphere of the brain.
Within the next weeks, a rapid deterioration and cerebellar symptoms could be detected. The patient developed a rapidly progressive dementia. CSF analysis was positive for 14-3-3 protein. According to these results the patient was diagnosed with probable sCJD. The patient died 37 days after the initial diagnosis. The autopsy of the brain confirmed the diagnosis of sCJD.
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Fig. 1: DWI reveals high signal in the left caudate nucleus (arrow) and slightly in the cortical regions of the frontal and temporal lobe.
We report a 52-year-old female patient who was admitted to hospital because of tremor and changed mental status. The onset of symptoms was three months ago. Furthermore the patient suffered from dysphagia and ataxia.
MRI revealed symmetric restriction of diffusion in the caudate nucleus, putamen, thalami and cortical in the frontal and temporal lobes (Fig. 2 and Fig. 3). FLAIR sequence showed high signal in putamen and caudate nucleus (Fig. 4). CSF analysis was positive for 14-3-3 protein but EEG examination did not show any clear lesions. However, the patient fulfilled the criteria for probable sCJD. She deteriorated within a few weeks and could not swallow anymore. So a percutaneous endoscopic gastrostomy (PEG) was performed. The patient did not show up for follow up examination. Autopsy was not available in this case.
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Fig. 2: DWI with symmetric hyperintense signal alteration in the putamen, caudate nucleus and thalami.