Diffuse metabolic changes in the brain of patients with familial amyloid polyneuropathy. A proton MRSI study.
OBJECTIVE
To assess brain metabolic abnormalities in patients with familial amyloid polyneuropathy (FAP) due to the transthyretin (TTR) gene mutations.


BACKGROUND
The TTR-FAP has variable phenotypic expression, which includes abnormalities of the central nervous system (CNS). Several conventional MRI studies have shown brain abnormalities, probably secondary to amyloid accumulation in leptomeningeal and subarachnoid vessels. However, TTR-related amyloid deposits do not seem to significantly affect the brain parenchyma and a prominent CNS impairment is considered to be rare in TTR amyloidosis.


METHODS
We performed proton MR spectroscopic imaging (1H-MRSI) in the central brain of four unrelated TTR-FAP patients with either minimal or no signs of neurological involvement and eight age- and sex-matched normal controls (NC). Metabolic changes were assessed in the entire volume of interest (VOI) and in the frontal, periventricular and posterior white matter (WM).


RESULTS
Conventional MRI was normal in 2 patients and showed minimal WM lesions in the remaining 2 patients. 1H-MRSI showed N-acetylaspartate to creatine ratio (NAA/Cr) decreases in the central brain VOI in all TTR-FAP patients (p < 0.005). These NAA/Cr decreases were homogeneous in all WM regions (p < 0.05 for all).


CONCLUSIONS
1H-MRSI findings suggest that diffuse metabolic changes, probably related to axonal damage, are present in brains of TTR-FAP patients even when they have no or minimal clinical and MRI signs of CNS involvement. The mechanism leading to sub-clinical metabolic brain changes needs to be identified.
Mazzeo
Anna
A
Department of Neuroscience, Psychiatry and Anaesthesiology, University of Messina, Italy.
Toscano
Antonio
A
Stromillo
Maria L
ML
Battaglini
Marco
M
Messina
Corrado
C
Federico
Antonio
A
Vita
Giuseppe
G
De Stefano
Nicola
N
D000328:Adult; D028227:Amyloid Neuropathies, Familial / Q000378:metabolism* / Q000473:pathology; D001224:Aspartic Acid / Q000031:analogs & derivatives / Q000378:metabolism; D001369:Axons / Q000473:pathology; D001923:Brain Chemistry / Q000502:physiology*; D003401:Creatine / Q000378:metabolism; D005260:Female; D006801:Humans; D008279:Magnetic Resonance Imaging; D008297:Male; D008875:Middle Aged; D011228:Prealbumin / Q000235:genetics*
D011228:Prealbumin; D001224:Aspartic Acid; C000179:N-acetylaspartate; D003401:Creatine