Probable Creutzfeldt-Jakob Disease Mimicking a Perioperative Stroke in an Elderly Adult.

Abstract

To the Editor: A case of sporadic Creutzfeldt-Jakob disease (CJD) occurring in a 76-year-old admitted to the hospital for a fall-related wrist fracture woman is reported. Three hours after surgery and admission to the Perioperative Geriatric Care Unit, she was diagnosed with a dysarthria, but physical examination was not completed because of pain, recent anesthesia and postoperative confusion. Brain magnetic resonance imaging (MRI), performed immediately to exclude stroke, showed bilateral symmetrical hyperintensities within the anterior striatum and anteromedial thalami on fluid-attenuated inversion recovery and diffusion-weighted imaging (DWI) sequences (Figure 1). She presented with a 3-month history of increasing disability associated with repeated falls. Physical examination revealed cerebellar ataxia, extrapyramidal and pyramidal signs, and myoclonus. Taken together, history and clinical and radiological findings suggested CJD. MRI performed 1 month earlier for repeated falls showed identical abnormalities, but diagnosis was not made at that time. During hospitalization, electroencephalography (EEG) was normal. Cerebrospinal fluid (CSF) analysis showed negative 14–3-3 protein and a high tau total protein level (886 pg/mL, normal range 100–450 pg/mL). A search for genetic mutations in the prion protein gene (M129V) was negative, excluding a genetic form of CJD. The woman was informed of the probable diagnosis, and psychological support was provided for her and her family. According to her wishes, and despite increasing fall risk, she went home with assistance but was readmitted 24 hours later, after a fall, and then was admitted to a nursing home. Her situation worsened, with an increase in extrapyramidal signs and cognitive disorders. She was admitted to a palliative care unit and died 5 months after her initial admission to the Perioperative Geriatric Care Unit. CJD is a rare, fatal, neurodegenerative disease that occurs in one per million people. Definitive diagnosis requires neuropathological findings including pathogenic protease resistant protein accumulation characterized by spongiform changes, neuronal loss, and reactive astrocytic proliferation, with or without amyloid plaques. Eighty percent of cases are sporadic, 10% to 15% are genetic or familial, and 1% are acquired. The World Health Organization proposed clinically relevant CJD criteria in 19981 that were upgraded in 2009 with the addition of MRI criteria.2 Diagnosis of CJD in elderly adults has rarely been reported. CJD should be suspected in the case of rapidly progressive dementia with neurological signs or in conjunction with repeated falls and with neurological signs such as pyramidal syndrome, cerebellar ataxia, extrapyramidal syndrome with myoclonus, visual disturbances, or akinetic mutism.1, 2 In the current case, diagnosis of CJD was particularly challenging in the postoperative period because confusion, pain, and recent anesthesia limited clinical examination, which was made mainly according to MRI. The importance of MRI has been reported in the literature for CJD diagnosis and to exclude differential diagnoses such as other dementia or stroke. In 50% of cases, hyperintensities are observed in the caudate nucleus, the putamen, and the cerebellar cortex (T2, fluid-attenuated inversion recovery, and DWI sequences). The pulvinar sign is suggestive of variant CJD.3 DWI has been shown to be the most sensitive MR sequence.4, 5 DW-MRI may show CJD-associated lesions 3 weeks after symptoms with high sensitivity (91%) and specificity (95%),5, 6 although studies suggest that up to 80% of these abnormalities are missed,3 like in the current case, despite previous MRI, illustrating that awareness of MRI features of CJD is insufficient. In the current case, all other complementary investigations were inconclusive. EEG can show polymorphic and repetitive slower wave discharges, characteristic bi- or triphasic paroxysmal waves, or spike-slow waves in 60% of cases,7 but these abnormalities occur intermittently, and sensitivity of EEG periodic sharp wave complexes is only 66% with 74% specificity.8 With 88% sensitivity and 72% specificity, a negative CSF 14–3-3 assay does not exclude CJD, depending on of the evolution of the disease and disease subtype.9, 10 Several biomarkers, including tau protein, neurospecific enolase, and S100b protein, have attracted great interest. CSF tau protein had better diagnostic accuracy than other protein detection, with 91% sensitivity and 88% specificity.9 In the current case, a search for prion protein gene mutation was performed for several reasons. Two of the woman's children were alive, family history was missing, and clinical signs and course of the genetic form of the disease are usually comparable with those of the sporadic form. Geriatricians should recognize clinical and paraclinical signs of CJD, but diagnosis remains challenging. The clinical presentation can mimic dementia or stroke, but MRI, EEG, and biomarkers can assist in the diagnosis. According to international criteria, this woman had probable CJD, but no autopsy was performed. Conflict of Interest: The editor in chief has reviewed the conflict of interest checklist provided by the authors and has determined that the authors have no financial or any other personal conflicts with this paper. Author Contributions: All authors contributed to this paper. Sponsor's Role: None.