Background Huntington's disease (HD) is pathologically characterised by a selective neurodegeneration of vulnerable populations of neurons, with an early marked neuronal loss and atrophy in the neostriatum. Dopaminergic innervations of neostriatal neurons originate in the substantia nigra pars compacta. Few studies have investigated the neuronal loss and the functional role of the substantia nigra in HD. Neuropathological and neurochemical studies provide conflicting results, with the evidence of neuronal loss varying from minimal loss to 40%. The few imaging studies evidenced a reduction of striatal DAT uptake and vescicular monoamine transporter type-2 (VMAT2). No correlations with clinical data have yet been investigated.
Aims We have evaluated in vivo the integrity of nigrostriatal projections in genetically confirmed HD patients and determined whether their clinical and neuropsychiatric features are correlated with the dopamine transporter (DAT) levels.
Methods 12 HD patients and 12 controls, age matched, underwent SPECT scans with 123I-FP-CIT, a tracer that selectively binds to DAT, following an adequate drug washout. The association between clinical aspects (age of onset, duration and severity of disease, mean number of triplets, severity of involuntary movements and bradykinesia), neuropsychological assessment (verbal and visuospatial memory, attentive, executive and abstractive capacities), neuropsychiatric features (NeuroPsychiatry Inventory Scale) and striatal DAT uptake (ROI approach analysis) was explored.
Results Striatal (p<0.05), caudate (p<0.05) and putaminal (p<0.01) uptake was significantly lower in patients with respect to controls. No correlation between striatal uptake and clinical or neuropsychological features was found.
Conclusions Reduced striatal DAT binding suggests nigrostriatal pathology in HD that could be related to substantia nigra degeneration. The absence of any correlation with age of onset, disease duration and severity and the number of triplets suggests that nigrostriatal pathology occurs early in the course of the disease. Also, the lack of any kind of correlation between clinical, neuropsychological and neuropsychiatric features with striatal DAT uptake suggests that motor and both psychiatric and cognitive aspects in HD are not related to nigrostriatal degeneration.
- Huntington disease
- substantia nigra
- 123I-FP-CIT SPECT
Statistics from Altmetric.com
If you wish to reuse any or all of this article please use the link below which will take you to the Copyright Clearance Center’s RightsLink service. You will be able to get a quick price and instant permission to reuse the content in many different ways.