The Role of Dual-Phase 18 F-FP-CIT PET to Early Diagnosis of Corticobasal Syndrome.

BACKGROUND: Corticobasal syndrome (CBS) is a neurodegeneration characterized by asymmetric parkinsonism, dystonia, myoclonus, and apraxia. In the early stage, CBS presents with asymmetric parkinsonism and cortical symptoms (apraxia and alien hand), and neuroimaging finding is often vague, making early clinical differentiation from idiopathic Parkinson disease (IPD) challenging. This study was performed to delineate the specific patterns of cortical hypoperfusion, dopamine transporter (DAT) uptake using dual-phase FP-CIT PET in discriminating between CBS and IPD at early stage. PATIENTS AND METHODS: The study enrolled clinically diagnosed CBS (n = 11) and IPD (n = 22) patients (age and sex matched). All participants underwent dual-phase 18 F-FP-CIT PET, and regional SUV ratio (SUVR) was obtained by semiquantitative analysis. The early perfusion imaging and DAT imaging were compared between groups. RESULTS: The regional SUVRs (early phase) of the frontal lobe, thalamus, cingulate, and caudate were significantly lower in patients with CBS, whereas the SUVR of occipital lobe was lower in the IPD group. The CBS group exhibited more prominent asymmetry than the IPD group, particularly in the perirolandic area, superior frontal gyrus, and anterior parietal lobe in early phase PET. Striatal DAT uptake (delayed phase) revealed that the caudate showed lower SUVR and prominent asymmetry in the CBS group, and the caudate-to-putamen ratio (CP ratio) was significantly lower in CBS patients ( P < 0.001). Among the parameters (early and delayed), the CP ratio in DAT exhibited the most powerful discriminative power from receiver operating characteristic curve comparison (area under curve = 0.983). CONCLUSIONS: This study demonstrated that the dual-phase FP-CIT PET is useful in differentiating CBS and IPD in the early stage of the disease, and a lower CP ratio of DAT imaging is highly informative for distinguishing between corticobasal degeneration and IPD.

Comparative Olfactory Profiles in Parkinson's Disease and Drug-Induced Parkinsonism.

OBJECTIVE: Drug-induced parkinsonism (DIP) is a frequently encountered diagnostic possibility when considering Parkinson's disease (PD). While olfactory dysfunction is a common clinical feature in PD, the comparison of olfactory function between the two conditions remains insufficient. This study aimed to compare olfactory function, including threshold, discrimination, and identification (TDI) profiles, between PD and DIP. METHODS: Consecutive patients with drug-naïve PD (n = 78) or DIP (n = 31) confirmed through dopamine transporter imaging were enrolled in this study. The YSK olfactory function (YOF) test, composed of TDI domains culturally familiar odorants to Koreans, was administered to all patients. RESULTS: In the study population, patients with DIP were significantly older than patients with PD. Over 70% of patients in each group had hyposmia or anosmia, and there was no significant difference in the occurrence of olfactory dysfunction between the two groups. In addition, there were no differences in the total YOF score and threshold score between the two groups. Meanwhile, the PD group had a significantly lower discrimination and identification score than the DIP group after adjusting for age, sex, the existence of diabetes, disease duration, and cognitive function. CONCLUSION: This study demonstrated that detailed olfactory profiles are different in PD and DIP, even though olfactory dysfunction can be observed in both conditions.

Scaling problem in Parkinson's disease patients with pain.

INTRODUCTION: Although pain is common in Parkinson's disease (PD), the underlying mechanism remains unknown. Scaling function and dopaminergic hypofunction may contribute to pain development because increased pain sensitivity is observed in PD and is normalized after levodopa administration. We aimed to determine whether spatial discrimination (SD) and striatal dopaminergic activity (DA) differed between PD patients with and without pain. METHODS: We divided 90 patients with drug-naïve PD into two groups based on the presence or absence of pain and compared the SD threshold (SDT). We evaluated the correlation of the SDT with pain severity in PD with pain. We also compared the DA of 48 patients and analyzed the correlation with pain severity in PD patients with pain. RESULTS: The SDTs did not differ between the two groups, but unmeasurable SDT was more frequent in PD with pain. There was a positive correlation of pain severity with the SDT of the more affected hand but no correlation with the SDT of the less affected hand. The DA did not differ between the groups. There was a negative trend of pain severity with the DA of the ventral striatum (VS) but no correlation with the other striatal subregions. CONCLUSIONS: Pain in PD may be associated with scaling dysfunction in the sensory system. The abnormal scaling function would render the PD patient hypersensitive to even mild pain. The dopamine in the VS appears to be associated with pain severity; however, the relationship of striatal dopaminergic deficits with pain occurrence requires further investigation.

Subthalamic deep brain stimulation improves vascular endothelial function in Parkinson's disease.

OBJECTIVES: Vascular health (white matter change, vascular risk factor, angiogenesis, microvascular alteration) is associated with clinical progression or levodopa-induced dyskinesia in PD. Vascular endothelial function is known to reflect the earliest vascular change. While DBS can improve motor and non-motor symptoms, the effect of DBS on vascular endothelial function is unknown. Thus, we aimed to investigate whether DBS surgery could impact vascular endothelial function in PD. METHOD: A total of 20 PD patients were recruited. Vascular endothelial function was evaluated with flow-mediated dilation (FMD). FMD was investigated before and after one year of DBS surgery. RESULTS: FMD improved (6.01 ± 1.58 to 6.84 ± 1.57, p = 0.027). While the level of homocysteine slightly decreased (13.8 ± 4.1 to 13.0 ± 3.2, p = 0.05), there was no significant correlation between FMD changes and homocysteine levels (r = 0.42, p = 0.065). FMD change was associated with baseline age (r = -0.59, p = 0.006) but not with disease duration (p = 0.73), baseline UPDRS III (p = 0.81), change of UPDRS III and dyskinesia, and LEDD change (p = 0.94). Multivariate linear regression analysis revealed that only age (B = -0.139; p = 0.024) was significantly and inversely correlated with the change of FMD. CONCLUSIONS: We found that STN-DBS improves vascular endothelial function in PD. Further studies are needed to clarify the exact pathogenesis and clinical implication of beneficial effects on vascular endothelial dysfunction in PD.

Sonoanatomy of the platysmal bands: What causes the platysmal band?

BACKGROUND: The platysmal band is created by the platysma muscle, a thin superficial muscle that covers the entire neck and the lower part of the face. The platysmal band appears at the anterior and posterior borders of the muscle. To date, no definite pathophysiology has been established. Here, we observed a lack of knowledge of the anatomy of the platysma muscle using ultrasonography in this study. METHODS: We conducted a descriptive, prospective study observing the platysmal band in resting and contraction states to reveal muscle changes. Twenty-four participants (aged 23-57 years) with anterior and posterior neck bands underwent ultrasonography in resting and contracted states. Ten cadavers were studied aged 67-85 years to measure the thickness of the platysma muscle at 12 points: horizontally (medial, middle, lateral) and vertically (inferior mandibular margin, hyoid bone, cricoid cartilage, superior margin of clavicle). RESULTS: The anterior and posterior borders of the platysma muscle were thicker than the middle of the platysma muscle when in a contracted state, and the muscle also had a convex shape when contracted. The thickness of the platysma muscle was not significantly different over 12 points in the resting state. During contraction, the platysma muscles contracted in the medial and lateral margins of the muscle, which was more significant in the posterior bands. CONCLUSION: The anterior and posterior platysmal bands are related to muscle thickness during contraction. These observations support the change in platysmal band treatment only at the anterior and posterior border of the muscle.

Neurofilament light chain and cardiac MIBG uptake as predictors for phenoconversion in isolated REM sleep behavior disorder.

BACKGROUND: Isolated rapid-eye-movement (REM) sleep behavior disorder (iRBD) is considered as a prodromal stage of either multiple system atrophy (MSA) or Lewy body disease (LBD; Parkinson's disease and dementia with Lewy bodies). However, current knowledge is limited in predicting and differentiating the type of future phenoconversion in iRBD patients. We investigated the role of plasma neurofilament light chain (NfL) and cardiac metaiodobenzylguanidine (MIBG) uptake as predictors for phenoconversion. METHODS: Forty patients with iRBD were enrolled between April 2018 and October 2019 and prospectively followed every 3 months to determine phenoconversion to either MSA or LBD. Plasma NfL levels were measured at enrollment. Cardiac MIBG uptake and striatal dopamine transporter uptake were assessed at baseline. RESULTS: Patients were followed for a median of 2.92 years. Four patients converted to MSA and 7 to LBD. Plasma NfL level at baseline was significantly higher in future MSA-converters (median 23.2 pg/mL) when compared with the rest of the samples (median 14.1 pg/mL, p = 0.003). NfL level above 21.3 pg/mL predicted phenoconversion to MSA with the sensitivity of 100% and specificity of 94.3%. Baseline MIBG heart-to-mediastinum ratio of LBD-converters (median 1.10) was significantly lower when compared with the rest (median 2.00, p < 0.001). Heart-to-mediastinum ratio below 1.545 predicted phenoconversion to LBD with the sensitivity of 100% and specificity of 92.9%. CONCLUSIONS: Plasma NfL and cardiac MIBG uptake may be useful biomarkers in predicting phenoconversion of iRBD. Elevated plasma NfL levels may suggest imminent phenoconversion to MSA, whereas low cardiac MIBG uptake suggests phenoconversion to LBD.

Deep brain stimulation in Parkinson disease with valosin-containing protein gene mutation.

BACKGROUND AND PURPOSE: Mutations in the gene encoding valosin-containing protein (VCP) are related to myriad medical conditions, including familial amyotrophic lateral sclerosis, inclusion body myopathy, and frontotemporal dementia. There are several reports of a link between these mutations and early onset Parkinson disease (PD). CASE DESCRIPTION: We report a 53-year-old PD patient with VCP mutation who later developed motor complications, thus receiving subthalamic nucleus deep brain stimulation (DBS) at the age of 56 years. However, myopathy emerged 1.5 years after surgery. CONCLUSIONS: With the phenotype variability of VCP, DBS should be carefully evaluated, considering the possible unfavorable long-term outcomes due to other symptoms of this mutation.

Cortical mean diffusivity is reliable in measuring brain abnormalities in drug-naïve essential tremor patients.

OBJECTIVE: Essential tremor (ET) is a common movement disorder, but the pathogenesis is poorly understood. Several associated brain areas were reported with inconsistent results due to heterogeneous populations. It is necessary to analyze a more homogeneous patient group. METHODS: We recruited 25 drug-naïve ET patients and 36 age- and sex-matched controls. All participants were right-handed. ET. ET was defined according to diagnostic criteria of the Consensus Statement of the Movement Disorder Society on Tremor. ET patients were divided into sporadic (SET) and familial ET (FET). We assessed tremor severity in ET. The cortical microstructural changes were compared between ET patients and controls using mean diffusivity (MD) of diffusion tensor imaging, and cortical thickness. The correlation of tremor severity with the cortical MD and thickness were respectively analyzed. RESULTS: MD values were increased in the insular, precuneus, medial orbitofrontal, posterior, and isthmus cingulate and temporo-occipital areas in ET. In comparison between SET and FET, MD values were higher in the superior and caudal middle frontal, postcentral, and temporo-occipital regions in FET. The cortical thickness of ET patients was more increased in the left lingual gyrus and lower in the right bankssts gyrus. We could not find any correlation of tremor severity with the MD values in ET patients. Still, there was a positive correlation with the cortical thickness of the frontal and parietal areas. CONCLUSIONS: Our results support the idea that ET is a disorder that disrupts widespread brain regions and indicates that cortical MD may be more sensitive to measure brain abnormalities than cortical thickness.

Retinal Thickness and Its Interocular Asymmetry Between Parkinson's Disease and Drug-Induced Parkinsonism.

BACKGROUND: Drug-induced parkinsonism (DIP) is common, but diagnosis is challenging. Although dopamine transporter imaging is useful, the cost and inconvenience are problematic, and an easily accessible screening technique is needed. We aimed to determine whether optical coherence tomography (OCT) findings could differentiate DIP from Parkinson's disease (PD). METHODS: We investigated 97 de novo PD patients and 27 DIP patients using OCT and [18F] N-(3-fluoropropyl)-2b-carbon ethoxy-3b-(4-iodophenyl) nortropane (FP-CIT) positron emission tomography. We compared peripapillary retinal nerve fiber layer thickness (pRNFLT) and macular retinal thickness (mRT) between PD and DIP patients as well as interocular differences in the pRNFLT and the mRT. Asymmetric index (%) for retinal thickness (AIRT) was calculated to measure the interocular differences between pRNFLT and mRT. The correlation between AIRT and total striatal specific/non-specific binding ratio asymmetry index (SNBRAI) was investigated in PD and DIP patients. RESULTS: No significant differences in pRNFLT and mRT values were observed between PD and DIP patients (all P values > 0.090). The mean SNBRAI was significantly higher in PD than in DIP (P = 0.008) patients; however, AIRT did not differ between PD and DIP patients in pRNFLT and mRT (all P values > 0.100). SNBRAI did not correlate with AIRT of pRNFL or mRT in PD and DIP patients (all P values > 0.060). CONCLUSION: Our study showed no benefit of retinal thickness and interocular asymmetry measurements using OCT for distinguishing PD from DIP in the early stages. Additional investigations are needed for confirmation.

The effect of levodopa treatment on vascular endothelial function in Parkinson's disease.

OBJECTIVE: There has been increasing awareness that micro-vascular alteration or vascular inflammation has been associated with levodopa-induced dyskinesia in PD. Vascular endothelial function assessed by flow mediated dilation (FMD) is known to reflect early microvascular change. We compare the impact of levodopa or dopamine agonist treatment on the change of FMD in de novo PD patients. METHODS: This retrospective study used a selected sample from registry. We identified de-novo PD patients who underwent FMD at baseline, and follow-up FMD after 1 year (± 2 month) of levodopa (n = 18) or dopamine agonist (n = 18) treatment. RESULTS: FMD decreased after levodopa (8.60 ± 0.46 to 7.21 ± 0.4, p = 0.002) but there were no significant changes after DA treatment (8.33 ± 0.38 to 8.22 ± 0.33, p = 0.26). Homocysteine rose (11.52 ± 0.45 to 14.33 ± 0.68, p < 0.05) during levodopa treatment, but dopamine agonist had no effect (10.59 ± 0.38 to 11.38 ± 0.67, p = 0.184). Correlation analysis revealed that the changes in homocysteine level had non-significant correlation with FMD change (r = - 0.30, p = 0.06). FMD change was not associated with age (p = 0.47), disease duration (p = 0.81), baseline motor UPDRS (p = 0.43), motor UPDRS change (p = 0.64), levodopa equivalent dose change (p = 0.65). CONCLUSIONS: We found that 1-year levodopa treatment may adversely affect vascular endothelial function in de novo PD. Further studies are needed to clarify the exact pathogenesis and clinical implication of levodopa-induced endothelial dysfunction in PD.

Dual-phase 18 F-FP-CIT positron emission tomography and cardiac 123 I-MIBG scintigraphy of Parkinson's disease patients with GBA mutations: evidence of the body-first type?

BACKGROUND AND PURPOSE: Parkinson's disease (PD) with glucocerebrosidase (GBA) gene mutation (GBA-PD) is known to show more rapid clinical progression than sporadic PD without GBA mutation (sPD). This study was performed to delineate the specific patterns of cortical hypoperfusion, dopamine transporter uptake and cardiac meta-iodobenzylguanidine (MIBG) uptake of GBA-PD in comparison to sPD. METHODS: Through next-generation sequencing analysis targeting 41 genes, a total of 16 GBA-PD and 24 sPD patients (sex, age matched) were enrolled in the study, and the clinical, dual-phase [18 F]-N-(3-fluoropropyl)-2ß-carboxymethoxy-3ß-(4-iodophenyl) nortropane (1 8 F-FP-CIT) positron emission tomography (PET) and cardiac 123 I-MIBG scintigraphy results were compared between the two groups. RESULTS: The GBA-PD group had higher rates of rapid eye movement sleep behavior disorder, orthostatic hypotension and neuropsychiatric symptoms than the sPD group. Early-phase 18 F-FP-CIT PET showed significantly lower standard uptake value ratio on bilateral posterior parietal cortex (0.94 ± 0.05 vs. 1.02 ± 0.04, p = 0.011) and part of the occipital cortex (p < 0.05) in the GBA-PD group than the sPD group. In striatal dopamine transporter uptake, the regional standard uptake value ratio, asymmetry index and caudate-to-putamen ratio were similar between the two groups. The GBA-PD group had a lower heart-to-mediastinum uptake ratio in 123 I-MIBG scintigraphy than the sPD group. CONCLUSIONS: The GBA-PD patients showed decreased regional perfusion in the bilateral posterior parietal and occipital cortex. Cardiac sympathetic denervation and non-motor symptoms (orthostatic hypotension, rapid eye movement sleep behavior disorder) were more common in GBA-PD than sPD. These findings suggest that GBA-PD patients have more widespread peripheral (extranigral) α-synuclein accumulation, representing a body-first PD subtype.

Initial Vestibular Function May Be Associated with Future Postural Instability in Parkinson's Disease.

BACKGROUNDS: We aimed to understand the association between initial vestibular function examination and postural instability (PI) development in Parkinson's disease (PD). METHODS: After screening 51 PD patients, we divided 31 patients into 2 groups based on the presence of PI at the follow-up visit and compared the clinical features and vestibular-evoked myogenic potential (VEMP) variables. RESULTS: The mean values of Hoehn and Yahr stage, Unified Parkinson's Disease Rating Scale (UPDRS) part III, and item 30 (postural stability) of UPDRS were larger in patients with PI at a follow-up visit (p = 0.000, 0.006, 0.048, respectively). In VEMP analyses, the onset latencies of left and right cervical VEMPs were significantly reduced in patients with PI (p = 0.013, 0.040, respectively). CONCLUSION: We found that the initial VEMP test may be associated with later postural imbalance in PD, suggesting the baseline evaluation may help predict future PI occurrence. A more significant number of patients and more long-term follow-ups are likely to be required for confirmation.