VCOM Carolinas Research Day 2023

Clinical Case-Based Reports

Creutzfeldt-Jakob Disease: A Case Report Rishit J. Patel, BS; Paul LaPenna, DO Edward Via College of Osteopathic Medicine-Carolinas; Bon Secours Neurology Clinic at St. Francis Downtown

Abstract # CBR-4



- PMHx: coronary artery disease, hypertension, stroke, lacunar infarcts, paroxysmal atrial fibrillation, and diverticulosis of colon with hemorrhage - PSHx: aortic valve replacement and cataract removal; (-) hx of neurosurgery, corneal transplant, or neurological surgeries - FHx: stroke on paternal side, kidney disease on his maternal side, and dementia for his sister; no familial history of rapidly progressive neurological conditions - SHx: married; from Charleston, SC - denies use of tobacco products; no recent travel outside the country; denies consumption of wild game; denied receiving a blood transfusion ; endorses donating blood about 10 years prior to his visit; reports venison consumption in past - Physical Exam - (+) poor comprehension; motor apraxia; word-finding difficulties; minimal ataxia; dystonic posture of both feet; personality changes - Inability to perform delayed-recall test

Creutzfeldt-Jakob disease (CJD) is a rare form of human prion diseases. Spontaneous CJD (sCJD) is the most common variant, and often occurs in clusters. Common clinical findings include neuropsychiatric manifestations, startle myoclonus, cerebellar dysfunction, extrapyramidal symptoms and corticospinal involvement. Centers for Disease Control and Prevention (CDC) criteria for a definitive diagnosis requires a use of standard neuropathological techniques, immunocytochemically, Western blot confirmed protease-resistant PrP; and/or presence of scrapie-associated fibrils. However, a probable diagnosis can be made based on neuropsychiatric symptoms in addition to a positive RT-QuIC in CSF or other tissues. This case presentation is of a 75-year male who initially presented with 7-month history of rapidly progressive dementia. He had memory impairment, ataxia, and personality change with a positive RT-QuIC which supported the diagnosis of probable sCJD. The patient also had tremors and myoclonus present on the exam. The symptoms progressed dramatically, but then steadied out for a period. Unfortunately, the patient passed away from aspiration pneumonia 11 months after the onset of symptoms. The patient’s MRI showed cortical ribboning on right temporal lobe as well as posterior cingulate gyrus bilaterally. Post-mortem examination of brain tissue would have been vital to understand the etiology, the patient's family did not consent to it. - intermittent unintentional weight loss - decreased WBC count of 2.5 x109/L - CSF sample: - (-) IgG Index, Oligoclonal Banding, Neuronal Nuclear Antibodies, and VDRL - (+) RT-QuIC; increase concentration of T-tau protein and 14-3-3 gamma protein - MRI - May 2022: some abnormal cortical signals involving the right temporal lobe and bilateral posterior cingulate without cortical swelling or abnormal intracranial enhancement (Image 1a, 1b). - Mild degree of scattered and confluent foci of T2/FLAIR hyperintensity within periventricular and deep white matter which is often associated with small vessel ischemic change - June 2022: signal abnormalities in the contralateral left temporal lobe, right anterior parafalcine frontal lobe, small remote lacunar infarct in the right thalamus and right parietal lobe - Electroencephalogram (EEG) - mild left temporal abnormality; cortical dysfunction in his temporal region which may be consistent with an underlying ictal propensity Case Presentation - 75-year-old Caucasian male who was admitted in June 2022 for intermittent episodes of instability and dizziness - approximately 6 months and occur in a paroxysmal fashion

References 1. Manix M, Kalakoti P, Henry M, et al. Creutzfeldt-Jakob disease: updated diagnostic criteria, treatment algorithm, and the utility of brain biopsy. Neurosurgical Focus FOC . 2015;39(5):E2-. doi:10.3171/2015.8.FOCUS15328 2. Nakatani E, Kanatani Y, Kaneda H, et al. Specific clinical signs and symptoms are predictive of clinical course in sporadic Creutzfeldt-Jakob disease. Eur J Neurol . 2016;23(9):1455-1462. doi:10.1111/ene.13057 3. Fragoso DC, Gonçalves Filho AL da M, Pacheco FT, et al. Imaging of Creutzfeldt-Jakob Disease: Imaging Patterns and Their Differential Diagnosis. RadioGraphics. 2017;37(1):234-257. doi:10.1148/rg.2017160075 4. Rabinovici GD, Wang PN, Levin J, et al. First symptom in sporadic Creutzfeldt-Jakob disease. Neurology . 2006;66(2):286-287. doi:10.1212/01.wnl.0000196440.00297.67 I would like to take this opportunity to thank the patient’s family for letting me write a case report. I would also like extend this to Dr. Paul LaPenna, DO for trusting me with this project. Disclosure Statement: None of the authors report conflicts of interest with commercial enterprises. Funding: This work did not receive any specific grant from any funding agency in the public, commercial, or not-for-profit sector. Acknowledgements This patient is one of three who were diagnosed with CJD within a span of 5 weeks. Unfortunately, biopsies were not performed on any of these brains to provide a definitive diagnosis in terms of the specific variant. The other diagnosed patients passed away a few months prior to the death of this patient. Symptoms progressed at a slower rate in this patient compared to the others, and there was a period when they remained steady. A case series which focuses on comparing these patients might be a useful endeavor in exploring the origin of this variant. Post-mortem examination of the brain tissue and observing pathological prion deposition is the only definitive way to diagnose CJD and classify it into one of its subtypes. A probable diagnosis can, however, be supported by atypical EEG, 14-3 3 CSF assay, high signal in caudate/putamen or at least two cortical brain regions on diffusion-weighted or fluid attenuated inversion recovery (FLAIR) MRI. This patient had a positive RT- QuIC in CSF which classifies him as “probable CJD” but does not meet the criteria for “definite CJD” (Table 1). Furthermore, cerebellar changes such as difficulty with balance and being more prone to falls supports the diagnosis. Additionally, changes in personality and behavior are consistent with CJD. Myoclonus and akinetic mutism were not noted on the physical examination. This patient passed away in October 2022 rom aspiration pneumonia, which is a common complication of many neurodegenerative disease as they often lose the ability to swallow. Paperwork was filled out for postmortem analysis by the National Prion Disease Pathology Surveillance Center at Case Western Reserve, but the family has decided to put this on hold.

Image 1 (a) Cortical ribboning can be noted in right temporal lobe. (b) A similar finding is also present bilaterally in the posterior cingulate gyrus of the brain.

Probable Neuropsychiatric disorder plus positive RT-QuIC in cerebrospinal fluid (CSF) or other tissues OR - Rapidly progressive dementia; and at least two out of the following four clinical features: 1.Myoclonus 2.Visual or cerebellar signs 3.Pyramidal/extrapyramidal signs 4.Akinetic mutism AND a positive result on at least one of the following laboratory tests - a typical EEG (periodic sharp wave complexes) during an illness of any duration - a positive 14-3-3 CSF assay in patients with a disease duration of less than 2 years - High signal in caudate/putamen on magnetic resonance imaging (MRI) brain scan or at least two cortical regions (temporal, parietal, occipital) either on diffusion-weighted imaging (DWI) or fluid attenuated inversion recovery (FLAIR) AND without routine investigations indicating an alternative diagnosis.


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