Understanding Essential Tremor: Progress on the Biological Front

Louis, Elan D.

doi:10.1007/s11910-014-0450-z

Cited by 27 publications

(33 citation statements)

References 97 publications

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“…Aside from the presence of brainstem Lewy bodies in some cases, brain changes are not evident in other brain regions in postmortem studies of ET [1,8,26]. These data serve to reinforce the notion that the cerebellum is the seat of disease in ET [27].…”

Section: Pathological Changes Are Restricted To the Cerebellum And Domentioning

confidence: 55%

Linking Essential Tremor to the Cerebellum: Neuropathological Evidence

Louis

2015

Cerebellum

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A fundamental question about essential tremor (ET) is whether its associated pathological changes and disease mechanisms are linkable to a specific brain region. To that end, recent tissue-based studies have made significant strides in elucidating changes in the ET brain. Emerging from these studies is increasing neuropathological evidence linking ET to the cerebellum. These studies have systematically identified a broad range of structural, degenerative changes in the ET cerebellum, spanning across all Purkinje cell compartments. These include the dendritic compartment (where there is an increase in number of Purkinje cell dendritic swellings, a pruning of the dendritic arbor, and a reduction in spine density), the cell body (where, aside from reductions in Purkinje cell linear density in some studies, there is an increase in the number of heterotopic Purkinje cell soma), and the axonal compartment (where a plethora of changes in axonal morphology have been observed, including an increase in the number of thickened axonal profiles, torpedoes, axonal recurrent collaterals, axonal branching, and terminal axonal sprouting). Additional changes, possibly due to secondary remodeling, have been observed in neighboring neuronal populations. These include a hypertrophy of basket cell axonal processes and changes in the distribution of climbing fiber-Purkinje cell synapses. These changes all distinguish ET from normal control brains. Initial studies further indicate that the profile (i.e., constellation) of these changes may separate ET from other diseases of the cerebellum, thereby serving as a disease signature. With the discovery of these changes, a new model of ET has arisen, which posits that it may be a neurodegenerative disorder centered in the cerebellar cortex. These newly emerging neuropathological studies pave the way for anatomically focused, hypothesis-driven, molecular mechanistic studies of disease pathogenesis.

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Section: Pathological Changes Are Restricted To the Cerebellum And Domentioning

confidence: 55%

Linking Essential Tremor to the Cerebellum: Neuropathological Evidence

Louis

2015

Cerebellum

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“…However, the relatively common occurrence of nonmotor symptoms such as cognitive, behavioral, and sleep disturbances in ET led to the replacement of the long‐held “benign” mono‐symptomatic model with a complex concept of ET (Bhalsing et al., 2014). The complexity of ET‐related pathology was supported by findings of cerebellar abnormalities and widespread brain neuro‐degeneration (Louis, 2014b, 2014c). The cerebello‐thalamo‐cortical network (Sharifi, Nederveen, Booij, & van Rootselaar, 2014) (cerebello‐thalamo‐cortical [CTC], also known as “tremor network”) has been proposed to play a substantial role in ET.…”

Section: Introductionmentioning

confidence: 93%

White matter measures correlate with essential tremor severity—A pilot diffusion tensor imaging study

et al. 2018

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BackgroundAn evolving pathophysiological concept of essential tremor (ET) points to diffuse brain network involvement, which emphasizes the need to investigate white matter (WM) changes associated with motor symptoms of ET.ObjectivesTo investigate ET‐related WM changes and WM correlates of tremor severity using tremor clinical rating scales and accelerometry.MethodsTract‐based spatial statistics (TBSS) approach was utilized to compare 3 Tesla diffusion tensor imaging (DTI) data from 12 ET patients and 10 age‐ and gender‐matched healthy individuals. Clinical scales, tremor frequency and amplitude as measured by accelerometry were correlated with DTI data.Results ET patients demonstrated mean (MD) and radial diffusivity (RD) abnormalities in tracts involved in primary and associative motor functions such as bilateral corticospinal tracts, the superior longitudinal fascicles, and the corpus callosum but also in nonmotor regions including the inferior fronto‐occipital and longitudinal fascicles, cingulum bundles, anterior thalamic radiations, and uncinate fascicles. A combined tremor frequency and amplitude score correlated with RD and MD in extensive WM areas, which partially overlapped the regions that were associated with tremor frequency. No significant relationship was found between DTI measures and clinical rating scales scores.ConclusionsThe results show that ET‐related diffusion WM changes and their correlates with tremor severity are preferentially located in the primary and associative motor areas. In contrast, a relationship between WM was not detected with clinical rating scales. Accelerometry parameters may, therefore, serve as a potentially useful clinical measures that relate to WM deficits in ET.

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“…Despite its high prevalence, ET pathogenesis remains poorly understood. Clinicopathological and neuroimaging investigations in ET patients have pointed out different types of anomalies in the cerebellum that could be involved in tremor generation (Zeuner and Deuschl 2012;Louis 2014). For example, a reduction in the number of Purkinje cells (PC) together with axonal morphometric changes have been described in the cerebellum of a significant subgroup of ET patients Louis et al 2013), but PC loss was not detected in all ET studies Symanski et al 2014), possibly due to methodological differences (Louis and Faust 2014).…”

Section: Introductionmentioning

confidence: 99%