Clinical application of intrathecal gadobutrol for assessment of cerebrospinal fluid tracer clearance to blood.

BACKGROUNDMethodology for estimation of cerebrospinal fluid (CSF) tracer clearance could have wide clinical application in predicting excretion of intrathecal drugs and metabolic solutes from brain metabolism and for diagnostic workup of CSF disturbances.METHODSThe MRI contrast agent gadobutrol (Gadovist) was used as a CSF tracer and injected into the lumbar CSF. Gadobutrol is contained outside blood vessels of the CNS and is eliminated along extravascular pathways, analogous to many CNS metabolites and intrathecal drugs. Tracer enrichment was verified and assessed in CSF by MRI at the level of the cisterna magna in parallel with obtaining blood samples through 48 hours.RESULTSIn a reference patient cohort (n = 29), both enrichment within CSF and blood coincided in time. Blood concentration profiles of gadobutrol through 48 hours varied between patients diagnosed with CSF leakage (n = 4), idiopathic normal pressure hydrocephalus dementia (n = 7), pineal cysts (n = 8), and idiopathic intracranial hypertension (n = 4).CONCLUSIONAssessment of CSF tracer clearance is clinically feasible and may provide a way to predict extravascular clearance of intrathecal drugs and endogenous metabolites from the CNS. The peak concentration in blood (at about 10 hours) was preceded by far peak tracer enhancement at MRI in extracranial lymphatic structures (at about 24 hours), as shown in previous studies, indicating a major role of the spinal canal in CSF clearance capacity.FUNDINGThe work was supported by the Department of Neurosurgery, Oslo University Hospital; the Norwegian Institute for Air Research; and the University of Oslo.

Detailed visual assessment of striatal dopaminergic depletion in patients with idiopathic normal pressure hydrocephalus: unremarkable or not?

BACKGROUND: Dopamine transporter (DAT) imaging may enable clinicians to discriminate idiopathic normal pressure hydrocephalus (iNPH) from other parkinsonian disorders. However, a specific pattern of dopaminergic loss in DAT imaging of iNPH patients remains to be further elucidated. METHODS: In this preliminary study, 11 patients with iNPH in our hospital between March 2017 and February 2019 were finally enrolled. A diagnosis of iNPH was made according to the two established criteria. For visual analysis of DAT imaging, a striatum was divided into five domains. A semi-quantitative visual assessment was performed with a consensus between a nuclear medicine specialist and an experienced neurologist who were blinded to the clinical diagnosis. RESULTS: Striatal dopaminergic deficits were abnormal in 90.9% (10/11) of patients with iNPH. The degree of dopaminergic reduction was mild and heterogeneous. However, a tendency of preferential striatal DAT loss in the caudate nucleus (90.9%, 10/11) than in the putamen (72.7%, 8/11) was observed, whereas ventral portion (9.1%, 1/11) was relatively preserved. CONCLUSION: Striatal dopaminergic depletion might be mild and heterogeneous in patients with iNPH. These dopaminergic deficits were more common in the caudate nucleus than in the putamen, suggesting a pattern different from other degenerative parkinsonian disorders.

Regional cerebral metabolic rate of glucose evaluation and clinical assessment in patients with idiopathic normal-pressure hydrocephalus before and after ventricular shunt placement: a prospective analysis.

PURPOSE: We prospectively evaluated the regional cerebral metabolic rate of glucose (CMRglu) before and after ventricular shunt placement in idiopathic normal-pressure hydrocephalus (iNPH) patients, to investigate whether some brain regions are more involved than others; we also correlated the individual variations of CMRglu with the clinical scale score assessment after shunting. METHODS: Twenty iNPH patients (12 men; mean age 73 ± 9 years) underwent clinical scale score assessment and F-FDG PET-CT before and 1 week after shunting. RESULTS: Before shunting, CMRglu values were similar in right and left brain regions, as well as after shunting. After shunting, 17 of 20 iNPH patients were clinically improved; all scale scores decreased, and CMRglu significantly increased in all regions (P < 10). In 3 of 20 iNPH patients, the symptoms persisted, the scale scores did not change, and CMRglu increased only in 3 regions: left frontal, left putamen, and right thalamus. Before shunting, no difference in global CMRglu between clinically improved (n = 17) and not improved (n = 3) iNPH patients was found. After shunting, a significant (P = 0.01) correlation between individual variations of CMRglu and clinical assessment was found. CONCLUSIONS: These findings confirm that iNPH is a disease involving all cerebral regions almost in the same way, and shunt procedure has a similar effect on regional cerebral metabolism almost in the same way. Individual variations of CMRglu are more important than absolute values and correlate with clinical status after shunting. Clinical improvement depends not only on the capability to restore the cerebrospinal fluid dynamic, but also on the ability of cerebral parenchyma to recover the metabolic function.