title: An autopsy-verified case of FTLD-TDP type A with upper motor neuron-predominant motor neuron disease mimicking MM2-thalamic-type sporadic Creutzfeldt-Jakob disease.
abstract: Here we report an autopsy-verified case of frontotemporal lobar degeneration (FTLD)-transactivation responsive region (TAR) DNA binding protein (TDP) type A with upper motor neuron-predominant motor neuron disease mimicking MM2-thalamic-type sporadic Creutzfeldt-Jakob disease (sCJD). A 69-year-old woman presented with an 11-month history of progressive dementia, irritability, insomnia, and gait disturbance without a family history of dementia or prion disease. Neurological examination revealed severe dementia, frontal signs, and exaggerated bilateral tendon reflexes. Periodic sharp-wave complexes were not observed on the electroencephalogram. Brain diffusion MRI did not reveal abnormal changes. An easy Z score (eZIS) analysis for99mTc-ECD-single photon emission computed tomography (99mTc-ECD-SPECT) revealed a bilateral decrease in thalamic regional cerebral blood flow (rCBF). PRNP gene analysis demonstrated methionine homozygosity at codon 129 without mutation. Cerebrospinal fluid (CSF) analysis showed normal levels of both 14-3-3 and total tau proteins. Conversely, prion protein was slowly amplified in the CSF by a real-time quaking-induced conversion assay. Her symptoms deteriorated to a state of akinetic mutism, and she died of sudden cardiac arrest, one year after symptom onset.  Despite the SPECT results supporting a clinical diagnosis of MM2-thalamic-type sCJD, a postmortem assessment revealed that this was a case of FTLD-TDP type A, and excluded prion disease. Thus, this case indicates that whereas a bilateral decreasing thalamic rCBF detected by99mTc-ECD-SPECT can be useful for diagnosing MM2-thalamic-type sCJD, it is not sufficiently specific. Postmortem diagnosis remains the gold standard for the diagnosis of this condition.
authors.affiliation: a Department of Neurology and Geriatrics , Gifu University Graduate School of Medicine , Gifu , Japan.
authors.forename: Yuichi
authors.initials: Y
authors.lastname: Hayashi
authors.affiliation: b Department of Neuropathology , Institute for Medical Science of Aging, Aichi Medical University , Nagakute , Japan.
authors.forename: Yasushi
authors.initials: Y
authors.lastname: Iwasaki
authors.affiliation: a Department of Neurology and Geriatrics , Gifu University Graduate School of Medicine , Gifu , Japan.
authors.forename: Akira
authors.initials: A
authors.lastname: Takekoshi
authors.affiliation: a Department of Neurology and Geriatrics , Gifu University Graduate School of Medicine , Gifu , Japan.
authors.forename: Nobuaki
authors.initials: N
authors.lastname: Yoshikura
authors.affiliation: c Department of Radiology , Gifu University Graduate School of Medicine , Gifu , Japan.
authors.forename: Takahiko
authors.initials: T
authors.lastname: Asano
authors.affiliation: b Department of Neuropathology , Institute for Medical Science of Aging, Aichi Medical University , Nagakute , Japan.
authors.forename: Maya
authors.initials: M
authors.lastname: Mimuro
authors.affiliation: a Department of Neurology and Geriatrics , Gifu University Graduate School of Medicine , Gifu , Japan.
authors.forename: Akio
authors.initials: A
authors.lastname: Kimura
authors.affiliation: d Department of Locomotive Rehabilitation Sciences . Nagasaki University Graduate School of Medicine , Nagasaki , Japan.
authors.forename: Katsuya
authors.initials: K
authors.lastname: Satoh
authors.affiliation: e Division of CJD Science and Technology, Department of Prion Research , Center for Translational and Advanced Animal Research on Human Diseases, Tohoku University School of Medicine , Sendai , Japan.
authors.forename: Tetsuyuki
authors.initials: T
authors.lastname: Kitamoto
authors.affiliation: b Department of Neuropathology , Institute for Medical Science of Aging, Aichi Medical University , Nagakute , Japan.
authors.forename: Mari
authors.initials: M
authors.lastname: Yoshida
authors.affiliation: a Department of Neurology and Geriatrics , Gifu University Graduate School of Medicine , Gifu , Japan.
authors.forename: Takashi
authors.initials: T
authors.lastname: Inuzuka
mesh_terms: D000368:Aged; D001344:Autopsy; D007562:Creutzfeldt-Jakob Syndrome / Q000175:diagnosis*; D004268:DNA-Binding Proteins / Q000378:metabolism*; D003937:Diagnosis, Differential; D005260:Female; D057174:Frontotemporal Lobar Degeneration / Q000175:diagnosis* / Q000378:metabolism / Q000473:pathology; D006801:Humans; D008279:Magnetic Resonance Imaging; D016472:Motor Neuron Disease / Q000175:diagnosis* / Q000378:metabolism / Q000473:pathology; D015899:Tomography, Emission-Computed, Single-Photon
chemical_list: D004268:DNA-Binding Proteins
keywords: MM2-thalamic-type sporadic Creutzfeldt-Jakob disease single photon emission computed tomography; TDP43; cerebral blood flow; frontotemporal dementia; motor neuron disease; thalamus