V180I genetic Creutzfeldt-Jakob disease with cardiac sympathetic nerve denervation masquerading as Parkinson's disease

Abstract

Rationale: Creutzfeldt-Jakob disease (CJD) with a point mutation of valine to isoleucine at codon 180 of the prion protein gene (V180I) is the most frequent form of genetic CJD in Japan. However, peripheral nerve involvement, especially cardiac sympathetic denervation, has not been investigated in cases with V180I genetic CJD. We herein report a genetically confirmed case of V180I genetic CJD presenting with parkinsonism and cardiac sympathetic nerve denervation. Patient concerns: The patient was a 79-year-old Japanese woman who presented with subacute progressive gait disturbance and cognitive impairment. Clinical diagnosis of Parkinson's disease (PD) with mild cognitive impairment was initially suspected based on parkinsonism, such as bradykinesia, rigidity and tremor, and reduced accumulation of cardiac meta-iodobenzylguanidine (MIBG) scintigraphy. Interventions: Based on parkinsonism and impaired cardiac MIBG findings, levodopa/decarboxylase inhibitor was administered up to 300 mg/day; however, her symptoms were not improved. Outcomes: Her motor and cognitive function progressively deteriorated. Diagnosis: Although the patient had no family history of CJD, genetic CJD was diagnosed according to extensive hyperintensities in the bilateral cortices on diffusion-weighted magnetic resonance images, positive tau protein and 14-3-3 protein in the cerebrospinal fluid and a V180I mutation with methionine homozygosity at codon 129 by prion protein gene analysis. Lessons: We should be aware that reduced uptake of cardiac MIBG scintigraphy in patients presenting with parkinsonism cannot confirm a diagnosis of PD. CJD should be considered when patients show a rapid progressive clinical course with atypical manifestations of PD.

Systematic Review of Clinical and Pathophysiological Features of Genetic Creutzfeldt–Jakob Disease Caused by a Val-to-Ile Mutation at Codon 180 in the Prion Protein Gene

“…Dopaminergic denervation in the basal ganglia causes extrapyramidal signs, such as rigidity of the extremities and akinesia [ 55 ], and extrapyramidal signs in V180I-gCJD have been described in several cases [ 18 , 19 , 31 , 33 , 37 , 38 , 39 , 40 ]. Pathological studies revealed spongiform changes in the basal ganglia and PrP deposition in some patients with V180I-gCJD [ 27 , 31 ].…”

“…Pathological studies revealed spongiform changes in the basal ganglia and PrP deposition in some patients with V180I-gCJD [ 27 , 31 ]. Levodopa, mainly used to treat Parkinson’s disease [ 56 ], was ineffective on extrapyramidal symptoms in V180I-gCJD [ 38 , 39 ], indicating postsynaptic dysfunction of the nigrostriatal pathway. Interestingly, previous case reports described two patients with V180I-gCJD who were misdiagnosed as having Lewy body disease due to extrapyramidal signs and the positivity of dopamine transporter (DAT)-single photon emission computed tomography (SPECT).…”