Rationale:
In genetic Creutzfeldt-Jakob disease (gCJD), V180I and M232R mutations in the prion protein gene are specifically found in Japanese patients. Patients with V180I are less likely to show a periodic sharp wave complex (PSWC) on EEG. M232R gCJD is classified into the slowly or rapidly progressive type and the latter is more likely to show PSWC. Further EEG findings have not yet been established. The purpose of this study is to analyze EEG findings in patients with V180I and those with M232R mutation and clarify their relationships with clinical stage and brain MRI findings.
Method:
We evaluated the clinical and laboratory findings such as age of onset, clinical stage, EEG, and MRI in patients with V180I and those with M232R who admitted to Yokohama City University Hospital or Yokohama City University Medical Center from 2012 to 2018. The clinical stage was defined as follows: stage 1, mild psychiatric and neurologic symptom; stage 2, mild myoclonus or dementia; stage 3, moderate to severe dementia or akinetic mutism. EEG findings were examined for frequency of background activity, the appearance of interictal nonepileptiform discharges (IINED), interictal epileptiform discharges (IIED), and PSWC. MRI findings were examined for atrophy and diffusion-weighted imaging (DWI) hyperintensities of the cortex and basal ganglia. EEG-MRI relationships were analyzed in pairs of EEG and MRI simultaneously recorded at the same clinical stage in each patient. The laterality of their abnormal findings was compared between EEG and MRI.
Results:
Ten patients with V180I and 6 patients with M232R were extracted from our database. We found 13 and 12 pairs of EEG-MRI in patients with V180I and M232R, respectively. The results were summarized in Table 1a (V180I) and 1b (M232R).
In patients with V180I, IIED and PSWC were not detected. IINED was detected in all 13 pairs, including recording at stage 1. All of 5 pairs with focal, lateralized, or bilateral asymmetrical IINED showed concordance of the laterality between IINED and hyperintensities in cerebral cortex but not in basal ganglia.
In patients with M232R, IINED was also detected in all 12 pairs, including recording at stage 1. All of 7 pairs with focal, lateralized, or bilateral asymmetrical IINED showed concordance between IINED and cortical hyperintensities but not basal ganglia hyperintensities in terms of the laterality. IIED was detected in 8 of 12 pairs. Six of 7 pairs with focal, lateralized, or bilateral asymmetrical IIED showed coincidence of the laterality between IIED and cortical hyperintensities. In 6 patients with M232R, PSWC was observed in 2 patients belonging to the rapidly progressive type.
Conclusion:
IIED and PSWC were not detected in patients with V180I. IINED was detected from stage 1 in both mutations. The concordance of the laterality was observed between cortical hyperintensities and IINED in both mutations and IIED in M232R mutation. Of note, the evaluation of IINED in an early stage may predict the laterality in DWI cortical hyperintensities.
Funding:
:none
FIGURES
Figure 1