Locus coeruleus degeneration and cerebellar gray matter changes in essential tremor

Lv, Dayao; Zhou, Cheng; Pu, Jiali; Lu, Jinyu; Zhao, Gaohua; Gu, Luyan; Guan, Xiaojun; Guo, Tao; Xu, Xiaojun; Zhang, Minming; Tian, Jun; Yin, Xinzhen; Zhang, Baorong; Zhao, Guohua; Yan, Yaping

doi:10.1007/s00415-022-11409-z

Cited by 7 publications

(6 citation statements)

References 32 publications

Supporting

Mentioning

Contrasting

Order By: Relevance

“…Compared to free-water imaging, NM-MRI is a preferable method for the assessment of LC impairment. Indeed, the aforementioned results are consistent with previous MRI studies [19,21,30] and post-mortem studies [31][32][33] demonstrating LC impairment in ET and PD. However, a smaller-scale study reported no significant difference in CNR LC between HC and ET patients, but a difference between ET and tremordominant PD (PD TD ) patients was observed [34].…”

Section: Discussionsupporting

confidence: 92%

“…However, advanced MRI techniques such as neuromelaninsensitive MRI (NM-MRI) and free-water imaging have emerged as important tools for in vivo assessment of LC injury. Currently, NM-MRI is considered the optimal noninvasive in vivo imaging modality, with which our team and other researchers have detected LC degeneration in patients with ET and PD [19,21]. Free-water imaging is a novel imaging technique for detecting LC degeneration with high sensitivity [22], and could therefore serve as a supplementary tool for evaluating LC injury.…”

Section: Introductionmentioning

confidence: 99%

See 1 more Smart Citation

Assessing the Role of Locus Coeruleus Degeneration in Essential Tremor and Parkinson’s Disease with Sleep Disorders

Liu,

Zhou,

Fang

et al. 2024

JPD

Self Cite

View full text Add to dashboard Cite

Background: Previous studies have demonstrated the importance of the locus coeruleus (LC) in sleep-wake regulation. Both essential tremor (ET) and Parkinson’s disease (PD) share common sleep disorders, such as poor quality of sleep (QoS). LC pathology is a feature of both diseases. A question arises regarding the contribution of LC degeneration to the occurrence of poor QoS. Objective: To evaluate the association between LC impairment and sleep disorders in ET and PD patients. Methods: A total of 83 patients with ET, 124 with PD, and 83 healthy individuals were recruited and divided into ET/PD with/without poor QoS (Sle/NorET and Sle/NorPD) subgroups according to individual Pittsburgh Sleep Quality Index (PSQI) score. Neuromelanin-sensitive magnetic resonance imaging (NM-MRI) and free-water imaging derived from diffusion MRI were performed. Subsequently, we evaluated the association between contrast-to-noise ratio of LC (CNRLC) and free-water value of LC (FWLC) with PSQI scores in ET and PD groups. Results: CNRLC was significantly lower in ET (p = 0.047) and PD (p = 0.018) than in healthy individuals, whereas no significant difference was found in FWLC among the groups. No significant differences were observed in CNR/FWLC between patients with/without sleep disorders after multiple comparison correction. No correlation was identified between CNR/FWLC and PSQI in ET and PD patients. Conclusions: LC degeneration was observed in both ET and PD patients, implicating its involvement in the pathophysiology of both diseases. Additionally, no significant association was observed between LC integrity and PSQI, suggesting that LC impairment might not directly relate to overall QoS.

show abstract

Section: Discussionsupporting

confidence: 92%

Section: Introductionmentioning

confidence: 99%

Assessing the Role of Locus Coeruleus Degeneration in Essential Tremor and Parkinson’s Disease with Sleep Disorders

Liu,

Zhou,

Fang

et al. 2024

JPD

Self Cite

View full text Add to dashboard Cite

show abstract

“…Postmortem changes are centered in and around Purkinje cells (PCs), with numerous studies demonstrating PC loss [16,32,36]. These data align well with considerable clinical and neuroimaging data that have linked ET to the cerebellum [5,15,19,24,[29][30][31]42] and which suggest that ET is neurodegenerative in nature [4,6,7,12,18,22,23,27,28,40,41,47,[50][51][52]. While neuroimaging studies have variably shown mild atrophy in the cerebellum or speci c cerebellar folia [2,13,17,49], or no detectable volumetric changes [10], the sense is that marked atrophy is not a clear feature of the ET cerebellum and that a search for a more suitable neuroimaging signature of neurodegeneration is in order.…”

Section: Introductionmentioning

confidence: 54%

Decreased Synaptic Vesicle Glycoprotein 2A Binding in the Human Postmortem Essential Tremor Cerebellum: Evidence of Reduction in Synaptic Density

Yang,

Zheng,

Chen

et al. 2023

Cerebellum

View full text Add to dashboard Cite

ObjectiveDespite being one of the most prevalent neurological diseases, the pathophysiology of essential tremor (ET) is not fully understood. Neuropathological studies have identi ed numerous degenerative changes in the cerebellum of ET patients, however. These data align with considerable clinical and neurophysiological data linking ET to the cerebellum. While neuroimaging studies have variably shown mild atrophy in the cerebellum, marked atrophy is not a clear feature of the cerebellum in ET and that a search for a more suitable neuroimaging signature of neurodegeneration is in order. Postmortem studies in ET have examined different neuropathological alterations in the cerebellum, but as of yet have not focused on measures of generalized synaptic markers. This pilot study focuses on synaptic vesicle glycoprotein 2A (SV2A), a protein expressed in practically all synapses in the brain, as a measure of synaptic density in postmortem ET cases. MethodsThe current study utilized autoradiography with the SV2A radioligand [ 18 F]SDM-16 to assess synaptic density in the cerebellar cortex and dentate nucleus in three ET cases and three age-matched controls. ResultsUsing [ 18 F]SDM-16, SV2A was 53% and 46% lower in the cerebellar cortex and dentate nucleus, respectively, in ET cases compared to age-matched controls. ConclusionFor the rst time, using in vitro SV2A autoradiography, we have observed signi cantly lower synaptic density in the cerebellar cortex and dentate nucleus of ET cases. Future research could focus on in vivo imaging in ET to explore whether SV2A imaging could serve as a much-needed disease biomarker.

show abstract

“…An identifiable cascade of pathological changes is one of the key hallmarks of diseases that lend themselves to staging schemes. The pathophysiology of ET has not been fully elucidated, although there is mounting postmortem evidence that it is neurodegenerative, with postmortem changes observed primarily in the cerebellar cortex [2,3,11,12,83]. While it is remains unclear as to whether these are the only changes in ET, and what the precise order of evolution of these changes is, some models have been proposed, suggesting a series of early changes that compromise the physical integrity and physiological function of Purkinje cells, subsequent changes that are likely reparative and regenerative, and then eventual cell death [2].…”

Section: Formulating a Staging Scheme For Et: Arguments In Favor Ofmentioning

confidence: 99%

“…Essential tremor (ET) is a chronic, progressive neurological disease; its prevalence in the population is high, making it one of the most common movement disorders among adults [1]. Recent evidence from clinical, neuroimaging, and postmortem studies suggest that the disease could be neurodegenerative [2][3][4][5][6][7][8][9][10][11][12][13][14][15][16][17][18]. Although in the past mislabeled as "benign" [19], the impact of ET on patients' as well as caregivers' lives can be significant [20][21][22][23][24][25][26][27], and this reinforces the importance of research that advances the field.…”

Section: Introductionmentioning

confidence: 99%

Developing a Staging Scheme for Essential Tremor: A Discussion of Organizing Principles

Lenka,

Louis

2023

Tremor and Other Hyperkinetic Movements

View full text Add to dashboard Cite

Essential tremor (ET) is a chronic, progressive neurological disease that may negatively affect patients' lives. While there has been considerable progress in ET research, some fundamental issues remain unaddressed. One such issue is disease staging. Staging schemes have inherent value and are part of the dialogue that clinicians have with other movement disorders patients. We highlight the value of and challenges with developing a staging system for ET and organize a discussion around the potential steps in developing such a system. Diseases for which there are staging schemes generally have a number of shared characteristics. ET has numerous features that would lend themselves to a staging scheme: emerging evidence supporting the existence of a premotor phase of disease, insidious onset, progressive worsening of arm tremor, spread of tremor to other body regions, the observation that patients seem to be at increased risk for other conditions within the same organ (i.e., emergence of Parkinson's disease and Alzheimer's disease in excessive numbers of ET patients), pathological changes in the cerebellum whose evolution can be ordered from (i) those that compromise the physical integrity and physiological function of Purkinje cells, (ii) subsequent changes that are reparative and regenerative, and (iii) eventual cell death. Challenges to formulating a staging scheme are the absence of both a biological marker and an "end stage" of disease. The sum of combined evidence suggests that a staging scheme would be of value. We provide initial thoughts as to how to begin to structure such a staging scheme.

show abstract

Locus coeruleus degeneration and cerebellar gray matter changes in essential tremor

Cited by 7 publications

References 32 publications

Assessing the Role of Locus Coeruleus Degeneration in Essential Tremor and Parkinson’s Disease with Sleep Disorders

Assessing the Role of Locus Coeruleus Degeneration in Essential Tremor and Parkinson’s Disease with Sleep Disorders

Decreased Synaptic Vesicle Glycoprotein 2A Binding in the Human Postmortem Essential Tremor Cerebellum: Evidence of Reduction in Synaptic Density

Developing a Staging Scheme for Essential Tremor: A Discussion of Organizing Principles

Contact Info

Product

Resources

About