Striatal 123I-Ioflupane SPECT abnormality in sporadic Creutzfeldt–Jakob disease

Abstract

A 61-year-old man presented with a 9 month history of progressive coordination, speech and memory problems as well as a 20 lb weight loss. He had fatigue, daytime somnolence and anxiety. Past personal and family medical histories were non-contributory. Examination demonstrated poor recall [Mini Mental State Examination (MMSE) 27/30, losing three points for memory]. He had an unsteady gait, could not tandem walk, had a fine upper limb postural tremor and had mild limb apraxia. The remainder of his neurological exam was normal. Investigations for a cerebellar syndrome were initiated. Full blood count, electrolytes, liver enzymes, B12, folate, thyroid-stimulating hormone (TSH), free T4, autoantibodies (mitochondrial, anti-gastric parietal cell, liver kidney microsomal, anti-smooth muscle, antinuclear antibody, anti-neutrophil cytoplasmic antibody), immunoglobulins, serum protein electrophoresis, copper, caeruloplasmin, manganese, neuronal antibodies (anti Ri, Yo, Hu), voltage-gated K channel antibodies, TSH receptor binding antibody and thyroid peroxisome antibodies were normal or negative. Cerebrospinal fluid (CSF) glucose and protein were normal, and there were no cells. The diagnosis of multiple system atrophy-cerebellar phenotype was considered. One year into the illness, dopamine transporter imaging (DAT) using 123I-Ioflupane single-photon emission computed tomography (SPECT) showed equivocally abnormal appearance qualitatively. After standard processing protocols, which involves attenuation correction during reconstruction, quantification of specific to non-specific ratios showed reduced caudate and putamen uptake bilaterally (see Fig. 1 for qualitative appearance and ratios), the right putamen having the lowest ratio. Subsequent brain magnetic resonance imaging (MRI) revealed T2 hyperintensity and corresponding restricted diffusion of the basal ganglia and thalami bilaterally as well as the cingulate gyri, right middle frontal gyrus and left parietal cortex, suggestive of sporadic Creutzfeldt–Jakob disease (CJD) (Fig. 2). Electroencephalogram (EEG) was normal. Within weeks, startle myoclonus developed, and he died shortly thereafter. Autopsy confirmed the diagnosis of sporadic CJD. A single published case of DAT in CJD also revealed reduced pre-synaptic putaminal uptake [1], and together with our case, suggests dopaminergic pathway dysfunction in CJD. These in vivo findings are in agreement with a recent pathologic study of the nigrostriatal pathway in sporadic CJD in which Vital et al. [2] found both preand post-synaptic cell loss in the nigrostriatal system. The loss of dopaminergic neurons in the substantia nigra correlated with the loss of neurons in the caudate and putamen. Interestingly, the patient previously reported by Ragno et al. [1] had an extrapyramidal syndrome while our patient had a cerebellar syndrome yet also had abnormal DAT imaging. In our patient, the DAT imaging appearance was not felt to be typical of idiopathic Parkinson’s disease. C. Hinnell M. Samuel (&) Department of Neurology, King’s College Hospital, 9th Floor, Ruskin Wing, Denmark Hill, London SE5 9RS, UK e-mail: m.samuel@nhs.net