J Neurol—melanin-sensitive magnetic resonance imaging studies reveal blue spot degeneration and cerebellar volume changes in patients with essential tremor

Essential tremor (ET) is the most common movement disorder, reported to affect more than 60 million people
worldwide.
Patients are characterized by postural/motor tremor of both upper extremities, which also affect the head, legs, arms, vocal cords, trunk, or other areas [1].

Because this definition is based on clinical features rather than etiology, ET is considered a tremor "syndrome" [1].

The neuropathological basis of ET is unclear, and studies have shown that there are two types of pathology: one with cerebellar variation with Purkinje cytopenia and one predominantly located in the blue spot (LC) [2-4].
of Lewy body denatured variants
.
At present, imaging studies of ET focus more on the cerebellum, and there is great heterogeneity in the study of cerebellar volume, suggesting the presence of extracerebellar changes, such as blue spots
.
The aim of this study was to use neuromelanin-sensitive imaging to detect the integrity of blue spots in ET patients and further explore its relationship
with motor symptoms and cerebellar volume.

Recently, Master Doctor Lv Dayao, Chief Physician Zhao Guohua of the Fourth Affiliated Hospital of Zhejiang University, Dr.
Zhou Cheng, Deputy Chief Physician Yan Yaping, Deputy Chief Physician Pu Jiali, Chief Physician Zhang Baorong of the Second Affiliated Hospital of Zhejiang University, etc.
published titles in the Journal of Neurology The research paper "Locus coeruleus degeneration and cerebellar gray matter changes in essential tremor" found that the blue spot signal value (the) in ET patients found that the blue spot signal value (the) in ET patients contrast-to-noise ratio of LC (CNR_LC) is lower than normal control (HC).

Further subgroup analysis showed that the patterns of blue spot and cerebellar volume changes were different between different ET subgroups, which were manifested by a significant decrease in blue spot integrity and cerebellar IV-V observed in the ET headless shaking group (nh-ET).
The leaflets increase
in volume.
Patients with ET and head tremor (h-ET) did not find a significant difference in CNR_LC, but showed cerebellar vermis IV-V and lobules VI atrophied significantly, and there was a significant negative correlation
between CNR LC and vermiform leaflet IV-V.
The results suggest that blue degeneration may be present in patients with ET
.
Both the blue spot and the cerebellum may be involved in the pathophysiological process
of ET.
Melanin-sensitive imaging may be an effective tool
for authors to further explore the pathophysiology of ET.

First, the study included a total of 53 cases from the Second Affiliated Hospital of Zhejiang University School of Medicine from March 2019 to December 2021 ET patients, 71 age- and education-matched healthy controls (HCs).

Demographic data for ET and control are shown in Table 1
.
All participants underwent a GE 3.
0TMR scan to acquire neuromelanin-sensitive magnetic resonance imaging and a T1 phase scan (Figure 1A-C).

Table 1: Demographic characteristics of subjects

(Source: DY Lv, et al.
, J Neurol, 2022).

The investigators used ITK-SNAP (https://sourceforge.
net/projects/itk-snap/) software to manually measure
the blue spot area of the subjects.
The location with the highest signal intensity (SI) and extending to the upper cerebellar foot in the three consecutive sections from the level of the hypothalamus is determined as LC.

Circular regions of interest (ROIs) are delineated in bilateral LCs and midpontine (PTs) of the same slice (as contrast regions)[5].

As shown in Figure 1, the ROI sizes of LC and PT are 2^mm2 and respectively 20mm²
。 The mean and standard deviation (SD) in bilateral LC and PT were calculated
.
CNR_LC is calculated using the following formula: CNR LC=(SI _LC− SI_PT)/ SD_PT
。 The results showed that there was a significant difference _{in CNR LC} between the ET group and the HC group
.
The CNR_LC of the ET group was lower than that of the HC group (p=0.
031, Figure 1 ，D）
。 LC is the main source of norepinephrine regulation in the brain, and it has a wide range of projections in the brain, including those of the cerebellum [6], and the norepinephrine-cerebellar junction is important for the normal function of cerebellar Purkinje cells [7]
。 Previous pathological studies have found Lewy body pathology
in LC.
8 out of 33 ET brains (24.
2%) have Lewy bodies in the brainstem, mainly in LC
。 While other ET brains (25/33, 75.
8%) do not have Lewy bodies, the cerebellum has pathological changes, including a decrease in Purkinje cells[3].

The above results suggest that LC may play a different role
than the cerebellum in the development of ET.
In addition, some imaging studies have shown that the clinical phenotype of ET is associated
with significant changes in brain morphology.
For example, ET patients with head tremor (h-ET) exhibit more pronounced patterns of cerebellar atrophy, while ET patients without head tremor do not notice significant changes [8-10].

。 These results suggest that the core pathology of nh-ET may not be cerebellar injury, and that other mechanisms such as LC degeneration may play a role
in the pathogenesis of nh-ET.

Figure 1: Differences
in anatomical location of blue spots and CNR LC in healthy control (HC) patients with essential tremor (ET).

(Source: DY Lv, et al.
, J Neurol, 2022).

Next, to understand LC and cerebellar changes in different ET subtypes, the researchers divided ET patients into 30 patients with head tremor (h-ET) and In 23 patients without head tremor (nh-ET), the CNR_LC in nh-ET was significantly lower HC (p=0.
016), but there was no significant difference
in the h-ET group.
SPM12 ( spm/software/ spm12/) and Dpabi (V6.
0_210501) software were used to feed subjects VBM analysis calculated the volume of gray matter in the cerebellum, and found that the IV-V and VI lobules of the cerebellar vermis in the h-ET group were atrophied The volume of the right cerebellar IV-V lobule increased in the nh-ET group (GRF corrected, p<0.
05, Figure 2 ）
。 These results suggest that the cerebellum plays a role
in ET.
Given the inhibitory effect of norepinephric on the cerebellum [7,11], it is reasonable to speculate that the increase in cerebellar GM volume in the nh-ET group is LC The result of
denaturation.
Therefore, both LC and the cerebellum may be involved in the pathophysiological process
of ET.

Figure 2: Gray matter volume differences
between ET, ET subgroup, and HC.
A: ET group compared with HC group; B: h-ET group compared with HC group; C: nh-ET group compared with HC group; D: h-ET group compared
to nh-ET group.

(Source: DY Lv, et al.
, J Neurol, 2022).

The correlation between the above difference regions as ROI and CNR LC was analyzed, and it was found that CNR _LC and vermicombi leaflets were found in the h-ET group There was a significant negative correlation between IV-V (r=-0.
651, p<0.
001, Figure 3
。 Based on this, the researchers speculate that LC and cerebellum may represent two aspects of ET pathogenesis, and there may also be a connection between them, which may be involved in the pathophysiological process
of ET.

Figure 3: Correlation analysis
of CNR LC and cerebellar IV-V gray matter volume in h-ET.
Sagittal (A), horizontal (B), and coronal images (C) of the ROI region and with CNR_LC Correlation analysis (D) is shown
in the figure above.

(Source: DY Lv, et al.
, J Neurol, 2022).