Multitracer PET imaging in a patient with Heidenhain variant of Creutzfeldt-Jakob disease

Objective: To assess whether positron emission tomography (PET) can be of diagnostic value and provide early insight into the course of Creutzfeldt-Jakob disease (CJD).

Background: We studied a 34-year old patient with probable Heidenhain variant of CJD. He presented with progressive impairment of stereoscopic vision (visus 0.5 L, 0.2 R), clumsiness of the right hand, fatigue and cognitive deterioration (initial MMSE 16/30, on reassessment 12/30). Liquor tested positive for neuron-specific enolase and 14–3-3 protein without evidence of inflammation. Flash and pattern reversal visual evoked potentials showed prolonged P100 time and decreased amplitudes bilaterally. Serial EEG recorded left aggravating temporo-occipital delta/theta-slowing, but no periodic sharp wave complexes.

Methods: We performed multitracer PET using [18F]-Fluoro-2-deoxy-D-glucose (FDG), [11C]-Flumazenil (FMZ) and 15O-H2O. Spatially normalized FMZ (using SPM99) and FDG (according to Herholz, 2002) were compared to age-matched controls. Additionally, FMZ images were normalized to white matter activity.

Results: In left temporo-parietal and bilateral occipital cortices, FDG images reveal severe metabolic impairment (14µmol/100g/min, global average 21µmol/100g/min). Blood flow, as assessed by H2O PET, and FMZ binding are reduced in the left parieto-parietal cortex with corresponding hyperintensity in diffusion-weighted MRI. Occipital cortices appear only slightly affected. Right-sided cerebellar metabolism and blood flow is reduced, indicating diaschisis due to reduced contralateral cerebral activity.

Discussion: CJD can only be diagnosed as „possible“ or „probable“ disease during lifetime, while definite diagnosis requires neuropathological examination. Substantiating a diagnosis of CJD during lifetime would be supportive regarding further therapeutic steps and patient guidance. FDG shows a pattern substantially different from Alzheimer, fronto-temporal and dementia with Lewy bodies. FMZ binding was only moderately reduced in severely hypometabolic regions. In conclusion, these findings suggest severe neuronal dysfunction and slight neurodegeneration in disease-affected regions. They provide additional information to EEG, EMG and laboratory results hardening probable diagnosis and should be evaluated in a greater patient collective.

Herholz et al. Neuroimage. 2002 Sep;17 (1):302–16.