This article requires a subscription to view the full text. If you have a subscription you may use the login form below to view the article. Access to this article can also be purchased.
Abstract
Objective: Inherited prion diseases are progressive neurodegenerative conditions, characterized by cerebral spongiosis, gliosis, and neuronal loss, caused by mutations within the prion protein (PRNP) gene. We wished to assess the potential of diffusion-weighted MRI as a biomarker of disease severity in inherited prion diseases.
Methods: Twenty-five subjects (mean age 45.2 years) with a known PRNP mutation including 19 symptomatic patients, 6 gene-positive asymptomatic subjects, and 7 controls (mean age 54.1 years) underwent conventional and diffusion-weighted MRI. An index of normalized brain volume (NBV) and region of interest (ROI) mean apparent diffusion coefficient (ADC) for the head of caudate, putamen, and pulvinar nuclei were recorded. ADC histograms were computed for whole brain (WB) and gray matter (GM) tissue fractions. Clinical assessment utilized standardized clinical scores. Mann-Whitney U test and regression analyses were performed.
Results: Symptomatic patients exhibited an increased WB mean ADC (p = 0.006) and GM mean ADC (p = 0.024) compared to controls. Decreased NBV and increased mean ADC measures significantly correlated with clinical measures of disease severity. Using a stepwise multivariate regression procedure, GM mean ADC was an independent predictor of Clinician's Dementia Rating score (p = 0.001), Barthel Index of activities of daily living (p = 0.001), and Rankin disability score (p = 0.019).
Conclusions: Brain volume loss in inherited prion diseases is accompanied by increased cerebral apparent diffusion coefficient (ADC), correlating with increased disease severity. The association between gray matter ADC and clinical neurologic status suggests this measure may prove a useful biomarker of disease activity in inherited prion diseases.
Glossary
- ADAS-Cog=
- Alzheimer's Disease Assessment Scale–Cognitive subscale;
- ADC=
- apparent diffusion coefficient;
- ADL=
- Barthel Activities of Daily Living scale;
- BET=
- brain extraction tool;
- BPRS=
- Brief Psychiatric Rating Scale;
- BSE=
- bovine spongiform encephalopathy;
- CDR=
- Clinician's Dementia Rating Scale;
- CGIS=
- Clinician's Global Impression of Disease;
- CI=
- confidence interval;
- DWI=
- diffusion-weighted imaging;
- FLAIR=
- fluid-attenuated inversion recovery;
- FOV=
- field of view;
- GM=
- gray matter;
- LC=
- left head of caudate;
- LP=
- left putamen;
- LPu=
- left pulvinar;
- MMSE=
- Mini-Mental State Examination;
- NBV=
- normalized brain volume;
- PH=
- peak height;
- PL=
- peak location;
- RC=
- right head of caudate;
- RP=
- right putamen;
- RPu=
- right pulvinar;
- ROI=
- region of interest;
- sCJD=
- sporadic Creutzfeldt-Jakob disease;
- TE=
- echo time;
- TI=
- inversion time;
- TR=
- repetition time;
- vCJD=
- variant Creutzfeldt-Jakob disease;
- WB=
- whole brain;
- WM=
- white matter.
AAN Members
We have changed the login procedure to improve access between AAN.com and the Neurology journals. If you are experiencing issues, please log out of AAN.com and clear history and cookies. (For instructions by browser, please click the instruction pages below). After clearing, choose preferred Journal and select login for AAN Members. You will be redirected to a login page where you can log in with your AAN ID number and password. When you are returned to the Journal, your name should appear at the top right of the page.
AAN Non-Member Subscribers
Purchase access
Letters: Rapid online correspondence
REQUIREMENTS
You must ensure that your Disclosures have been updated within the previous six months. Please go to our Submission Site to add or update your Disclosure information.
Your co-authors must send a completed Publishing Agreement Form to Neurology Staff (not necessary for the lead/corresponding author as the form below will suffice) before you upload your comment.
If you are responding to a comment that was written about an article you originally authored:
You (and co-authors) do not need to fill out forms or check disclosures as author forms are still valid
and apply to letter.
Submission specifications:
- Submissions must be < 200 words with < 5 references. Reference 1 must be the article on which you are commenting.
- Submissions should not have more than 5 authors. (Exception: original author replies can include all original authors of the article)
- Submit only on articles published within 6 months of issue date.
- Do not be redundant. Read any comments already posted on the article prior to submission.
- Submitted comments are subject to editing and editor review prior to posting.
You May Also be Interested in
Long-term Safety and Efficacy of Avalglucosidase Alfa in Patients With Late-Onset Pompe Disease
Dr. Marianne de Visser and Dr. Maudy Theunissen
► Watch
Alert Me
Recommended articles
Pathologic correlates of diffusion MRI changes in Creutzfeldt-Jakob disease
MRI identification of early white matter injury in anoxic–ischemic encephalopathy
Diffusion MRI shows increased water apparent diffusion coefficient in the brains of cirrhotics
Slowly progressive spread of the stroke-like lesions in MELAS