Essential Tremor versus “ET-plus”: A Detailed Postmortem Study of Cerebellar Pathology

Gionco, John; Hartstone, Whitney; Martuscello, Regina T.; Kuo, Sheng Han; Faust, Phyllis L.; Louis, Elan D.

doi:10.1007/s12311-021-01263-6

Cited by 30 publications

(24 citation statements)

References 34 publications

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“…Patients with midline tremors and tandem gait disorders had more cerebellar atrophy and more Purkinje cell axonal swellings with torpedo formation in the cerebellar vermis 32 . Although, a recent postmortem study has not demonstrated pathological differences in cerebellar cortex between ET and ET-plus cases 33 . With additional multiple soft signs, ET-plus patients may have a broader range of pathological lesions in the cerebello-thalamo-cortical circuit.…”

Section: Discussionmentioning

confidence: 86%

The differences in clinical characteristics and natural history between essential tremor and essential tremor plus

Lolekha

Dharmasaroja

Uransilp

et al. 2022

Sci Rep

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The diverse clinical manifestation of essential tremor (ET) has led to the question whether the different phenotypes may affect the clinical outcome and progression. This study aimed to estimate the clinical characteristics and natural history of ET and ET-plus. A total of 221 patients with ET were included, 117 (52.9%) reclassified as ET and 104 (47.1%) as ET-plus. Patients with ET-plus were significantly older in age at onset (P < 0.001); had a higher frequency of cranial tremors (P < 0.001), neurological comorbidities (P < 0.001) and psychiatric comorbidities (P = 0.025); more tremor progression (P < 0.001); and poorer response to medical treatment (P < 0.001) compared to ET patients. Regression analysis revealed that late-onset tremor (OR 11.02, 95% CI 2.79–43.53), neurological comorbidities (OR 3.38, 95% CI 1.56–7.31), psychiatric comorbidities (OR 4.29, 95% CI 1.48–12.44), cranial tremors (OR 2.10, 95% CI 1.02–4.30), and poor response to medical treatment (OR 3.67, 95% CI 1.87–7.19) were associated with ET-plus diagnosis. ET and ET-plus differ in the age of onset, tremor distribution, comorbidities, treatment response rate, and progression. Identifying the ET phenotypes may increase the clinical value in therapeutic strategies and clinical research in the future.

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Section: Discussionmentioning

confidence: 86%

The differences in clinical characteristics and natural history between essential tremor and essential tremor plus

Lolekha

Dharmasaroja

Uransilp

et al. 2022

Sci Rep

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“…One way to assess validity is to examine the stability of each putative subtype over time, as we have done here. Another way is to examine whether there are biological differences between the subgroups, as we have done previously ( 14 ).…”

Section: Discussionmentioning

confidence: 99%

“…On the other hand, the new classification has also engendered criticism and controversy, with considerable concern that it represents a disease stage rather than a true disease subtype ( 9 – 13 ). A recent postmortem study reported that the degenerative changes in the cerebellum that have been linked to ET did not differ between ET and ET plus, suggesting that the proposed new classification is not grounded in a biological difference ( 14 ).…”

Section: Introductionmentioning

confidence: 99%

“ET Plus”: Instability of the Diagnosis During Prospective Longitudinal Follow-up of Essential Tremor Cases

et al. 2021

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Background: A recent consensus statement introduced the term “ET plus”. Although investigators have quantified the prevalence of ET plus in cross-sectional studies, patients with ET plus have not been tracked longitudinally; hence, there is no understanding of its stability over time.Methods: We present prospective, longitudinal phenotypic data on an ET cohort that was followed regularly at 18-month intervals (T1, T2, T3, T4) for up to 64 months. We assigned an ET or ET plus diagnosis to each case at each time interval.Results: There were 201 participants at baseline. The proportion with ET plus increased from 58.7% at baseline to 72.1% at T4 (p = 0.046). Of 172 (85.6%) who received a diagnosis of ET plus at one or more time intervals, the diagnosis was unstable (e.g., with reversion) in 62 (36.0%). We also assessed the stability of the clinical features of ET plus. Rest tremor was the most unstable clinical feature of ET plus; it was present in 59 participants, among whom it reverted from present to absent in 23 (39.0%). By contrast, for “memory impairment” (i.e., either mild cognitive impairment or dementia), the proportion who reverted from present to absent was only 21.3%.Conclusion: These data support our two a priori hypotheses: (1) the prevalence of ET plus would increase progressively, as it likely represents a more advanced stage of ET, and (2) the ET plus diagnosis would not be stable over time, as cases would fluctuate with respect to their phenotypic features and their assigned diagnoses.

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“… 4 The most prominent criticism raised by some researchers against the construct of ET‐plus stands in the lack of pathological differences between ET and ET‐plus. 12 However, this criticism misinterprets that: (1) for neither tremor syndrome is there a generally accepted underlying pathology; and (2) that both ET and ET‐plus are currently viewed as syndromes rather than single diseases. 13 Nonetheless, the construct of ET‐plus has generated an enlightened debate about its validity, 12 , 14 with some researchers proposing that it could represent a later stage of ET based on the evidence that its defining characteristics vary as a function of disease duration.…”

Section: Clinical Conceptsmentioning

confidence: 99%

Milestones in Tremor Research: 10 Years Later

Erro

Fasano

Barone

et al. 2022

Movement Disord Clin Pract

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Major progress has occurred during the last decade in the field of tremor. From the clinical standpoint, a new classification has completely revised the nosology of tremor syndromes and has re‐conceptualized essential tremor as a syndrome rather than a single disease entity, fueling an ongoing enlightened debate. Significant advances have been obtained in terms of instrumental measurement of tremor, remarking on the possibility of developing novel treatment strategies based on tremor characteristics, namely tremor‐phase. Moreover, a better understanding of the pathophysiological mechanisms has further led to the suggestion of refining the classification of tremor syndromes according to their driving underpinnings. Finally, surgical options such as deep brain stimulation and focused ultrasound thalamotomy are now part of the therapeutic portfolio for tremor, but several oral drugs, including long‐chain alcohols, T‐channel blockers, allosteric modulators of potassium channels, and of GABA‐A receptors, are currently being tested and hold promise. This review will discuss the key milestones in tremor research of the last 10 years, with a focus on the most common tremor syndromes, namely essential tremor, dystonic tremor, and Parkinsonian tremor.

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Essential Tremor versus “ET-plus”: A Detailed Postmortem Study of Cerebellar Pathology

Cited by 30 publications

References 34 publications

The differences in clinical characteristics and natural history between essential tremor and essential tremor plus

The differences in clinical characteristics and natural history between essential tremor and essential tremor plus

“ET Plus”: Instability of the Diagnosis During Prospective Longitudinal Follow-up of Essential Tremor Cases

Milestones in Tremor Research: 10 Years Later

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