In this study, results of 18F-FP-CIT PET were abnormal in 90.9% (10/11) of enrolled iNPH patients, showing a remarkably heterogenous pattern. With regard to striatal subregions, a tendency of preferential striatal DAT loss in the caudate nucleus than that in the putamen was observed, whereas VS was relatively preserved. Additionally, a pattern of rostrocaudal gradient was found in the caudate nucleus and putamen, with the caudate nucleus being affected more than the putamen. These characteristics of presynaptic dopaminergic loss in iNPH are quite discernible from those in PD which tends to affect dorsal posterior putamen with relatively preserved caudate nucleus . To the best of our knowledge, this is the first study to report a specific pattern of DAT loss in iNPH patients using 18F-FP-CIT PET.
There have been a few reports investigating presynaptic dopaminergic deficit in hydrocephalic patients using different radiotracers. In a previous study using [11C]2-b-carbomethoxy-3b-(4-fluorophenyl) tropane, presynaptic dopaminergic loss was not found in iNPH patients . However, in that study, all enrolled patients had only mild severity of gait disturbance, which could be related to the relatively preserved dopaminergic function in the substantia nigra of the midbrain . In a study of Broggi et al. , 14 (46.5%) out of 30 iNPH patients with parkinsonism showed abnormal results in [123I]FP-CIT single photon emission computed tomography (SPECT) imaging, although subregional patterns of striatal dopaminergic loss were not described in that study. In a report of Allali et al. , 46.2% and 31.8% of iNPH patients showed abnormal [123I]FP-CIT SPECT by visual rating scale and semi-quantitative analysis, respectively. Although normal [123I]FP-CIT SPECT results on the basis of visual rating scale were not associated with a diagnosis of iNPH, normal results in the whole striatum by semi-quantitative analysis were associated with a diagnosis of iNPH. However, with respect to striatal subregions, normal caudate nucleus was not related to iNPH, while normal putamen was equivocal. In a case of obstructive hydrocephalus with shunt malfunction, abnormal 6-[18F]fluorodopa PET scan was found in the caudate nucleus and putamen with a relatively low caudate/posterior putamen ratio . These outcomes could support results of our study which revealed a high tendency of dopaminergic loss in the caudate nucleus and putamen, particularly in the PC of patients with iNPH.
Several hypotheses can be postulated for the presynaptic dopaminergic loss in iNPH patients. A few articles have demonstrated a morphological alteration of the midbrain in iNPH patients [4, 12]. As a consequence, an injury of the substantia nigra and/or striatum by abnormal pulsatile CSF flow can induce a dysfunction of the nigrostriatal pathway . Characteristics of the basal ganglia include high metabolic rate, distinctive microvasculature, and autoregulation. Other than PD and Parkinson-plus syndrome, diseases having structural lesions in the basal ganglia such as vascular parkinsonism and Fahr disease show presynaptic dopaminergic loss on DAT imaging and reduced cerebral blood flow in the basal ganglia on perfusion imaging [14, 15]. Likewise, regional cerebral blood flow is remarkably reduced in the caudate nucleus, putamen, and thalamus in iNPH patients . In addition, a decrease of glucose metabolism which shows high accordance rate with perfusion SPECT has been observed in the basal ganglia of a patient with iNPH [17, 18]. These findings suggest that the dysfunction or degeneration of basal ganglia could attribute to the pathophysiology of iNPH, in accordance with a neuropathological study .
Our preliminary study has several strengths and shortcomings. Firstly, we used 18F-FP-CIT PET known to be more sensitive than other DAT imaging tools including [123I]FP-CIT SPECT [18, 20]. To the best of our knowledge, a study investigating iNPH patients with 18F-FP-CIT PET has not been reported yet. Secondly, we used both the iNPH consensus guideline criteria and the Japanese iNPH guideline criteria for the exact diagnosis of iNPH in every patient [7, 8]. Thirdly, all patients underwent both MRI and DAT imaging. As for shortcomings of this study, firstly, the number of subjects was too small. Secondly, we used semi-quantitative visual assessment known to be less sensitive than automatic quantitative analysis. Thirdly, since none of our subjects underwent a postmortem examination, a possibility of the coexistence of iNPH and other parkinsonian neurodegenerative diseases might exist [21, 22].