Introduction
Search Strategy
Molecular Neuroimaging Correlates of Essential Tremor
Cerebral Blood Flow and Metabolism in Essential Tremor
Receptor and Neurotransmitter Imaging in Essential Tremor
Author, year | Technique | Cohort | Findings |
---|---|---|---|
Brooks et al. (1992) [19] | 18F-DOPA PET | 20 isolated PT 11 isolated RT 16 PD 20 HCs | 2 of 20 isolated PT had subnormal putamen 18F-DOPA activity, one of whom in the PD range and later became akinetic. 18 of 20 had normal tracer activity All isolated RT patients had putamen 18F-DOPA activity in the PD range |
Asenbaum et al. (1998) [26] | 123I-β-CIT SPECT | 32 ET (without soft signs) 29 PD (HY stage 1) 30 HCs | ET: normal striatal uptake compared to controls PD: reduced striatal uptake compared to controls |
Benamer et al. (2000) [21] | 123I-FP-CIT SPECT | 27 ET 158 parkinsonism 35 HCs | ET: 25 of 27 scans visually graded as normal Parkinsonism: 150 of 158 visually graded as abnormal HC: 33 of 35 visually graded as normal |
Parkinson Study Group (2000) [20] | 123I-β-CIT SPECT | 14 ET 43 PD 17 PSP 22 HCs | Visual inspection agreed with clinical diagnosis in: 98% of parkinsonism, 83% of ET/HCs Quantitative analysis did not find differences between ET and HCs (but found lower uptake in ET patients visually diagnosed as parkinsonism) |
Isaias et al. (2010) [24] | 123I-FP-CIT SPECT 99Tc-ECD SPECT (prefusion imaging) | 20 ET 13 PD 23 HCs | ET: normal striatal FP-CIT uptake at baseline and after 3 years. Some ET patients have caudate uptake lower than controls Tremor network analysis with perfusion imaging revealed significant and discriminant differences between ET and PD |
Roselli et al. (2010) [25] | 123I-FP-CIT SPECT (dopamine and serotonin transporter imaging) | 11 ET 15 PD, 16 LBD, 10 PSP 9 HC | ET: normal striatal and midbrain raphe FP-CIT uptake PD: reduced striatal and normal midbrain raphe FP-CIT uptake |
Di Giuda et al. (2012) [23] | 123I-FP-CIT SPECT | 15 ET 21 PD 17 HCs | ET: normal striatal uptake. Severity of anxiety symptoms inversely correlated with left caudate DAT PD: caudate DAT inversely correlated with depressive symptoms |
Author, year | Technique | Cohort | Findings |
---|---|---|---|
Lee et al. (1999) [27] | 123I-IPT SPECT | 9 isolated PT 6 PT and RT 11 PD 21 HCs | Isolated PT: normal striatal uptake PT and RT: uptake significantly lower than HCs and similar to PD PD: reduced striatal uptake |
Schwartz et al. (2004) [28] | 123I-FP-CIT SPECT | 10 ET with impairment at visuo-motor testing | Decreased striatal uptake in 8 of 10 patients. Striatal uptake correlated with visuo-motor testing score |
Ceravolo et al. (2008) [29] | 123I-FP-CIT SPECT | 61 patients with isolated atypical tremor (unilateral postural, rest o mixed tremor) | Rest tremor: abnormal DaT in 76%; of these, 75% progressed to PD after 2 years Postural tremor: abnormal DaT in 50%; of these, 50% progressed to PD after 2 years Mixed tremor: abnormal DaT in 50%; of these, 60% progressed to PD after 2 years No patient with normal baseline DaT progressed to PD after 2 years |
Novellino et al. (2009) [33] | 123I-FP-CIT SPECT 123I-MIBG cardiac SPECT | 10 ET 22 mixed (RT + PT) tremor + mild extrapyr features 20 PD 18 HCs | ET: normal striatal and cardiac uptake in all patients PD: reduced striatal and cardiac uptake in all patients Mixed tremor: 73% reduced striatal uptake; of these, 50% reduced cardiac MIBG uptake |
De Verdal et al. (2013) [30] | 123I-FP-CIT SPECT | 33 mixed tremor (RT + PT/KT) | Striatal DaT reduced in 76% of patients. No significant differences in tremor characteristics between patients with and without nigrostriatal denervation |
Coria et al. (2012) [31] | 123I-FP-CIT SPECT | 167 isolated action tremor (without RT or bradykinesia) | Asymmetric tremor in 74% of patients. Positive family history in 45% of patients Visually abnormal striatal DaT in 68% of patients; of these 91% had DaT in the range of PD. Onset of tremor > 50 years and asymmetrical distribution of tremor were predictive of nigrostriatal denervation |
Waln et al. (2015) [32] | 123I-FP-CIT SPECT | 22 ET “pure” 9 ET-P (ET + 1 PD cardinal sign) 8 ET + PD 13 HCs | ET “pure” and ET-P: normal DaT uptake by visual analysis. ET + PD visually abnormal Semiquantitative analysis: ET “pure” and ET-P had normal mean putamen and caudate SBR; non-significant reduction in caudate of ET compared to controls. ET-PD had reduced caudate and putamen SBR |
Molecular Neuroimaging Correlates of PD Tremor
Cerebral Blood Flow and Metabolism in PD Tremor
Author, year | Technique | Cohort | Findings |
---|---|---|---|
PET-FDG metabolic investigations | |||
Antonini et al. (1998) [49] | 18FDG PET | 8 PD with and 8 without tremor in off-state 10 HCs | PD with tremor had increased metabolic rate in a network comprising the thalamus, pons, and premotor cortical regions, a network that was called the PD related tremor pattern (PDTP) While all patients with PD usually express metabolic alterations in a metabolic network called PDRP, tremulous phenotype also require the expression of the PDTP |
Lozza et al. (2002) [89] | 18FDG PET | 17 non-demented PD in the ON state | Bradykinesia scores positively correlated with putaminal and pallidal metabolic rates. Tremor scores negatively correlated with putamen and cerebellar vermis metabolic rate |
Mure et al. (2011) [50] | 18FDG PET | 9 tremor dominant PD patients scanned at baseline and during Vim-DBS | Baseline metabolic pattern revealed a PD tremor-related network composed of cerebellum/dentate nuclei, primary motor cortex and striatum. Vim stimulation resulted in consistent reductions in this pattern expression. Without stimulation, pattern expression values correlated with accelerometric measurements of tremor amplitude |
Eggers et al. (2014) [51] | 18F-DOPA 18FDG PET | 64 PD patients (32 TD) | Higher putamen and caudate metabolism in tremulous PD vs akinetic-rigid PD. Striatal 18F-DOPA and FDG activity were closely correlated |
Serotonergic pathways investigations | |||
Doder et al. (2003) [69] | 11C-WAY 100,635 PET (5HT1A receptor ligand) | 23 PD 8 HCs | UDPRS total and rest tremor scores, but not bradykinesia and rigidity, were inversely correlated with tracer binding in midbrain raphe |
Caretti et al. (2008) [90] | 123I-beta-CIT (SERT ligand) | 32 PD (23 scanned also after 17 months) 13 HCs | PD with tremor have significantly reduced uptake in thalamus, representing mostly SERT availability, compared to PD without tremor; no differences at follow up (indicating greater declines in PD without tremor) |
Loane et al. (2013) [72] | 11C-DASB PET (SERT ligand) | 12 TD-PD 12 AR-PD 12 HCs | 11C-DASB uptake in putamen, caudate and raphe nuclei was negatively correlated with severity of action tremor, but not with rest tremor in TD-PD. TD-PD also showed SERT reductions in caudate and putamen compared to AR-PD |
Qamhawi et al. (2015) [70] | 123I-FP-CIT SPECT (SERT ligand) | 345 de novo PD 145 HCs | 123I-FP-CIT raphe uptake, representative of SERT availability, was inversely associated with rest tremor severity in the whole cohort and in a subgroup of tremulous patients |
Pasquini et al. (2018) [71•] | 123I-FP-CIT SPECT (SERT ligand) | 378 de novo PD 145 HCs | In TD patients rest tremor severity was inversely associated with raphe SERT at baseline and after two years. More severe raphe dysfunction coupled with less severe putaminal dopaminergic denervation was associated with higher rest tremor scores and reduced rest tremor response to dopaminergic therapy |
Noradrenergic pathways investigations | |||
Isaias et al. (2011) [74] | 123I-FP-CIT SPECT | 82 PD | 123I-FP-CIT binding in pons, representing locus coeruleus noradrenergic transporter, was significantly higher in PD patients than controls. No differences between patients with and without tremor |
Nahimi et al. (2018) [75] | 11C-MeNER PET (NET ligand) | 15 PD 10 HCs | Tracer uptake significantly reduced in red nucleus and thalamus of PD patients. Tremor occurrence was associated with higher thalamic tracer binding in PD. Tremor severity not associated with tracer binding in any region |
Kinnerup et al. (2021) [76•] | 11C-MeNER PET (NET ligand) | 65 PD (28 tremulous) 28 HCs | Tracer uptake was significantly higher in LC and thalamus of tremulous patients. In tremulous patients LC tracer uptake was similar to controls, while in the raphe was significantly reduced. In non-tremulous patients, tracer uptake was significantly reduced in all regions compared to controls Rest tremor severity was associated with higher NET availability in median raphe, thalamus and red nuclei |