Related Experiment Videos
Metabolite abnormalities in progressive multifocal leukoencephalopathy by proton magnetic resonance spectroscopy
L Chang1, T Ernst, C Tornatore
1Department of Neurology, UCLA School of Medicine, Harbor-UCLA Medical Center, Torrance, CA 90509, USA.
Objective:
To evaluate progressive multifocal leukoencephalopathy (PML) lesions using proton magnetic resonance spectroscopy (1H MRS).
Design:
CSF polymerase chain reaction (PCR) detection for JC viral (JCV) DNA; MRI and localized 1H MRS in the PML lesions, normal-appearing contralateral brain regions (CONTRA), and in matched brain regions of normal subjects.
Setting:
University-affiliated medical center.
Patients Or Participants:
20 AIDS patients with clinical diagnosis of PML, 16 had tissue and/or CSF evidence of JCV infection; 20 age-matched normal subjects.
Main Outcome Measures:
Metabolites from 1H MRS: N-acetyl aspartate (NA), creatine (CR), choline-containing compounds (CHO), myoinositol (MI), glutamine/glutamate (GLX), lactate, and lipids.
Results:
CSF PCR for JCV DNA showed 86% sensitivity. MRI showed characteristic demyelinating lesions; commonest locations were frontal lobe and cerebellum. 1H MRS in the lesions showed decreased NA (-35%; p < 0.0001) and CR (-18%; p = 0.003), increased CHO (+28%; p = 0.0005), occasional increased MI, and excess lactate (15/20 lesions) and lipids (18/20). In the CONTRA, MRS showed trends for increased CR (+15%), CHO (+15%), MI (+13%), and lower GLX (-9%; p = 0.02). Six patients, studied longitudinally (4-18 months), showed progressive spectroscopic changes; two patients with longest survival showed the highest MI.
Conclusions:
These MRS findings are consistent with neuropathologic observations of neuronal loss, cell membrane and myelin breakdown, and increased glial activity in PML lesions. The CONTRA abnormalities may be due to remote effects of PML or direct HIV-1 infection. 1H MRS may be useful for characterization and follow-up evaluation of PML lesions.
Insights
Proton magnetic resonance spectroscopy (1H MRS) reveals characteristic metabolic changes in progressive multifocal leukoencephalopathy (PML) lesions. These findings, including decreased N-acetyl aspartate and increased choline, aid in PML diagnosis and monitoring.
Area of Science:
- Neuroimaging
- Neuropathology
- Biochemistry
Background:
- Progressive multifocal leukoencephalopathy (PML) is a severe demyelinating disease.
- Accurate diagnosis and monitoring of PML are crucial for patient management.
- Proton magnetic resonance spectroscopy (1H MRS) offers a non-invasive method to assess brain metabolites.
Purpose of the Study:
- To evaluate the utility of 1H MRS in characterizing PML lesions.
- To compare metabolic profiles of PML lesions with normal-appearing contralateral brain regions and healthy controls.
Main Methods:
- JC viral (JCV) DNA detection via CSF PCR.
- Magnetic Resonance Imaging (MRI) and localized 1H MRS were performed on PML lesions and control brain regions.
- Analyzed metabolites included N-acetyl aspartate (NA), creatine (CR), choline (CHO), myoinositol (MI), glutamine/glutamate (GLX), lactate, and lipids.
Main Results:
- CSF PCR for JCV DNA demonstrated 86% sensitivity.
- 1H MRS in PML lesions showed significantly decreased NA and CR, and increased CHO, lactate, and lipids.
- Contralateral regions exhibited trends of increased CR, CHO, MI, and decreased GLX.
- Longitudinal studies revealed progressive spectroscopic changes in PML lesions.
Conclusions:
- 1H MRS findings correlate with neuropathological hallmarks of PML, including neuronal loss and myelin breakdown.
- Abnormalities in contralateral regions suggest potential remote effects of PML or HIV-1 infection.
- 1H MRS is a valuable tool for characterizing and monitoring PML lesions.