Introduction
Essential tremor (ET) is the most common movement disorder among adults. Although ET has been recognized as a mono-symptomatic benign illness, reports of non-motor symptoms and ...non-tremor motor symptoms have increased its clinical heterogeneity. The neural correlates of ET are not clearly understood. The aim of this study was to understand the neurobiology of ET using resting state fMRI.
Methods
Resting state functional MR images of 30 patients with ET and 30 age- and gender-matched healthy controls were obtained. The functional connectivity of the two groups was compared using whole-brain seed-to-voxel-based analysis.
Results
The ET group had decreased connectivity of several cortical regions especially of the primary motor cortex and the primary somatosensory cortex with several right cerebellar lobules compared to the controls. The thalamus on both hemispheres had increased connectivity with multiple posterior cerebellar lobules and vermis. Connectivity of several right cerebellar seeds with the cortical and thalamic seeds had significant correlation with an overall score of Fahn-Tolosa-Marin tremor rating scale (FTM-TRS) as well as the subscores for head tremor and limb tremor.
Conclusion
Seed-to-voxel resting state connectivity analysis revealed significant alterations in the cerebello-thalamo-cortical network in patients with ET. These alterations correlated with the overall FTM scores as well as the subscores for limb tremor and head tremor in patients with ET. These results further support the previous evidence of cerebellar pathology in ET.
Updates in essential tremor Okelberry, Tyler; Lyons, Kelly E.; Pahwa, Rajesh
Parkinsonism & related disorders,
20/May , Volume:
122
Journal Article
Peer reviewed
Open access
Essential tremor (ET) is one of the most common tremor disorders and can be disabling in its affect on daily activities. There have been major breakthroughs in the treatment of tremor and ET is the ...subject of important ongoing research. This review will present recent advancements in the epidemiology, genetics, pathophysiology, diagnosis, comorbidities, and imaging of ET. Current and future treatment options in the management of ET will also be reviewed. The need for continued innovation and scientific inquiry to address the unmet needs of persons of ET will be highlighted.
•Essential tremor (ET) is a common condition, especially among people aged 65 years and older, and many ET cases in the general population are undiagnosed.•A single unifying model of pathophysiology leading to tremor generation is lacking and additional research is needed.•ET is associated with a wide range of important comorbidities, both neurologic and non-neurologic, which impact the lives of patients.•There is a substantial unmet need in the treatment of ET and several promising pharmacologic agents and devices are under investigation.
Deep brain stimulation (DBS) has become a widespread and valuable treatment for patients with movement disorders such as essential tremor (ET). However, current DBS treatment constantly delivers ...stimulation in an open loop, which can be inefficient. Closing the loop with sensors to provide feedback may increase power efficiency and reduce side effects for patients. New implantable neuromodulation platforms, such as the Medtronic Activa PC+S DBS system, offer important data sources by providing chronic neural sensing capabilities and a means of investigating dynamic stimulation based on symptom measurements. The authors implanted in a single patient with ET an Activa PC+S system, a cortical strip of electrodes on the hand sensorimotor cortex, and therapeutic electrodes in the ventral intermediate nucleus of the thalamus. In this paper they describe the effectiveness of the platform when sensing cortical movement intentions while the patient actually performed and imagined performing movements. Additionally, they demonstrate dynamic closed-loop DBS based on several wearable sensor measurements of tremor intensity.
Reduced diffusion along perivascular spaces in adults with Alzheimer's-disease-related-dementias has been reported and attributed to reduced glymphatic function.
To apply quantitative measures of ...diffusion along, and orthogonal to, perivascular spaces in a cohort of older adults with and without clinical symptoms of alpha-synuclein related neurodegeneration.
181 adults with Parkinson disease (PD) or essential tremor (ET) additionally sub-classified by the presence of cognitive impairment underwent 3 T MRI. Diffusion-tensor-imaging (spatial resolution = 2x2x2 mm; b-value = 1000 s/mm2; directions = 33) measures of diffusion (mm2/s) parallel and orthogonal to perivascular spaces at the level of the medullary veins, and the ratio of these measures (ALPS-index), were calculated. Regions were identified by a board-certified neuroradiologist from T1-weighted and T2-weighted MRI. Evaluations of motor impairment and mild cognitive impairment (MCI) were interpreted by a board-certified neurologist and neuropsychologist, respectively. Multiple regression with false discovery rate correction was applied to understand how diffusion metrics related to (i) disease category (PD vs. ET), (ii) cognition (MCI status), and (iii) white matter disease severity from the Fazekas score.
The ALPS-index was reduced in PD compared to ET participants (p = 0.037). No association between the ALPS-index and MCI status, but an inverse association between the ALPS-index and Fazekas score (p = 0.002), was observed. The ALPS-index was inversely associated with age (p = 0.007).
Diffusion aberrations near perivascular spaces are evident in patients with alpha-synuclein related neurodegenerative disorders, and are related to age and white matter disease severity.
•The DTI-ALPS method is purported to contain information related to glymphatic function.•ALPS-index scores are reduced in Parkinson patients compared to essential tremor patients.•Findings parallel prior results demonstrating reduced ALPS-index scores in Alzheimer's disease.•Altered perivascular fluid transport in PD may be a mechanism of underlying (α-synuclein) accumulation.
Essential tremor is one of the most common tremor syndromes. According to the recent tremor classification, tremor as a symptom is defined as an involuntary, rhythmic, oscillatory movement of a body ...part and is classified along two axes: axis 1—defining syndromes based on the clinical features such as historical features, tremor characteristics, associated signs, and laboratory tests; and axis 2—classifying the etiology (Bhatia et al., Mov Disord 33:75–87,
2018
). The management of this condition has two major approaches. The first is to exclude treatable etiologies, as particularly during the onset of this condition the presentation of a variety of etiologies can be with monosymptomatic tremor. Once the few etiologies with causal treatments are excluded, all further treatment is symptomatic. Shared decision-making with enabling the patient to knowledgeably choose treatment options is needed to customize the management. Mild to moderate tremor severity can sometimes be controlled with occupational treatment, speech therapy of psychotherapy, or adaptation of coping strategy. First-line pharmacological treatments include symptomatic treatment with propranolol, primidone, and topiramate. Botulinum toxin is for selected cases. Invasive treatments for essential tremor should be considered for severe tremors. They are generally accepted as the most powerful interventions and provide not only improvement of tremor but also a significant improvement of life quality. The current standard is deep brain stimulation (DBS) of the thalamic and subthalamic region. Focused ultrasound thalamotomy is a new therapy attracting increasing interest. Radiofrequency lesioning is only rarely done if DBS or focused ultrasound is not possible. Radiosurgery is not well established. We present our treatment algorithm.
Although essential tremor (ET) is commonly encountered in clinical practice, historically, there has been considerable disagreement as how to best define it, and now with a growing sense of its ...clinical complexity, how to best encapsulate it. Here, I draw attention to five issues of current uncertainty.
A PubMed search conducted on June 19, 2017 crossed “essential tremor” with 9 second search terms (e.g., definition, diagnosis).
There are several major issues of clinical and diagnostic uncertainty. Underlying each issue is a larger question about the nature of the underlying pathophysiology of ET. Does age of onset of ET matter? How much dystonia is acceptable in ET? How much in the way of “cerebellar signs” are acceptable? Are non-motor features due to the underlying disease or merely secondary to the clinical features? Is ET a single disease entity or something else?
We are learning more about ET and, as a by-product of these efforts, are struggling with its definition. Further understanding the nature of the underlying disease pathogenesis as well as the role the cerebellum and cerebellar relays play in this process will likely provide important clues to enable us to bring order to areas of uncertainty.
SEE MOLL AND ENGEL DOI101093/AWW308 FOR A SCIENTIFIC COMMENTARY ON THIS ARTICLE: Brain regions dynamically engage and disengage with one another to execute everyday actions from movement to decision ...making. Pathologies such as Parkinson's disease and tremor emerge when brain regions controlling movement cannot readily decouple, compromising motor function. Here, we propose a novel stimulation strategy that selectively regulates neural synchrony through phase-specific stimulation. We demonstrate for the first time the therapeutic potential of such a stimulation strategy for the treatment of patients with pathological tremor. Symptom suppression is achieved by delivering stimulation to the ventrolateral thalamus, timed according to the patient's tremor rhythm. Sustained locking of deep brain stimulation to a particular phase of tremor afforded clinically significant tremor relief (up to 87% tremor suppression) in selected patients with essential tremor despite delivering less than half the energy of conventional high frequency stimulation. Phase-specific stimulation efficacy depended on the resonant characteristics of the underlying tremor network. Selective regulation of neural synchrony through phase-locked stimulation has the potential to both increase the efficiency of therapy and to minimize stimulation-induced side effects.
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