Anatomical texture patterns identify cerebellar distinctions between essential tremor and Parkinson's disease.
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ABSTRACT:
SUBMITTER: Hett K
PROVIDER: S-EPMC8090778 | biostudies-literature |
REPOSITORIES: biostudies-literature
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Project description:The neuronal physiological correlates of clinical heterogeneity in human essential tremor are unknown. We now test the hypothesis that thalamic neuronal and EMG activities during intention essential tremor are similar to those of the intention tremor which is characteristic of cerebellar lesions. Thalamic neuronal firing was studied in a cerebellar relay nucleus (ventral intermediate, Vim) and in a pallidal relay nucleus (ventral oral posterior, Vop) during stereotactic surgery for the treatment of tremor. Nine patients with essential tremor were divided clinically into two categories: one with a substantial component of tremor with intention (termed intention ET) and the other without (postural ET). These types of essential tremor were compared with patients having intention tremor plus other clinical signs of cerebellar disease (cerebellar tremor). Neurons in patients with either intention ET or cerebellar tremor had lower firing rates and lower spike×EMG coherence than those in patients with postural ET. Patients with intention ET had a lower spike×EMG phase lead than those with postural ET. Overall, thalamic activity measures of intention ET were different from postural ET but not apparently different from those of cerebellar tremor. One patient with the intention ET (number 4) had a good response to a left thalamotomy and then suffered a right cerebellar hemispheric infarct five years later. After the stroke the intention ET recurred, which is consistent with our hypothesis that intention ET is similar to that of the intention tremor which is characteristic of cerebellar lesions.
| S-EPMC3889719 | biostudies-literature
Project description:Background and purposeHand tremor is one of the most frequent symptoms in movement disorders, and differential diagnoses for hand tremor include Parkinson's disease (PD) and essential tremor (ET). However, accurately differentiating between PD and ET in clinical practice remains challenging in patients presenting with hand tremor. We investigated whether a questionnaire-based survey could be useful as a screening tool in patients with hand tremor.MethodsA questionnaire related to hand tremor consisting of 12 items was prospectively applied to patients with PD or ET in three movement-disorder clinics. Each question was analyzed, and a query-based scoring system was evaluated for differentiating hand tremors between PD and ET.ResultsThis study enrolled 24 patients with PD and 25 patients with ET. Nine of the 12 questions differed significantly between PD and ET: 1 about resting tremor, 4 questions about action tremor, and 4 about asymmetry. A receiver operating characteristics curve analysis revealed that the 9-item questionnaire showed a good discrimination ability, with a sensitivity of 88% and a specificity of 84%.ConclusionsThe developed Hand Tremor Questionnaire might be a good screening tool for hand tremors in patients with PD and ET.
| S-EPMC6031988 | biostudies-literature
Project description:Symptoms of essential tremor (ET) are similar to those of Parkinson's disease (PD) during their initial stages. Presently, there are few stable biomarkers available on a neuroanatomical level for distinguishing between these two diseases. However, few investigations have directly compared the changes in brain volume and assessed the compensatory effects of a change in the parts of the brain associated with PD and with ET. To determine the compensatory and/or degenerative anatomical changes in the brains of PD and ET patients, the present study tested, via two voxel-based morphometry (VBM) approaches (Basic vs. DARTEL VBM processing), the anatomical brain images of 10 PD and 10 ET patients, as well as of 13 age-matched normal controls, obtained through a 3T magnetic resonance scanner. These findings indicate that PD and ET caused specific patterns of brain volume alterations in the brains examined. In addition, our observations also revealed compensatory effects, or self-reorganization, occurring in the thalamus and the middle temporal gyrus in the PD and ET patients, due perhaps in part to the enhanced thalamocortical sensorimotor interaction and the head-eye position readjustment, respectively, in these PD and ET patients. Such a distinction may lend itself to use as a biomarker for differentiating between these two diseases.
| S-EPMC3682128 | biostudies-literature
Project description:BackgroundThe differential diagnosis between patients with essential tremor (ET) and those with Parkinson's disease (PD) whose main manifestation is tremor may be difficult unless using complex neuroimaging techniques such as 123I-FP-CIT SPECT. We considered that using smartphone's accelerometer to stablish a diagnostic test based on time-frequency differences between PD an ET could support the clinical diagnosis.MethodsThe study was carried out in 17 patients with PD, 16 patients with ET, 12 healthy volunteers and 7 patients with tremor of undecided diagnosis (TUD), who were re-evaluated one year after the first visit to reach the definite diagnosis. The smartphone was placed over the hand dorsum to record epochs of 30 s at rest and 30 s during arm stretching. We generated frequency power spectra and calculated receiver operating characteristics curves (ROC) curves of total spectral power, to establish a threshold to separate subjects with and without tremor. In patients with PD and ET, we found that the ROC curve of relative energy was the feature discriminating better between the two groups. This threshold was then used to classify the TUD patients.ResultsWe could correctly classify 49 out of 52 subjects in the category with/without tremor (97.96% sensitivity and 83.3% specificity) and 27 out of 32 patients in the category PD/ET (84.38% discrimination accuracy). Among TUD patients, 2 of 2 PD and 2 of 4 ET were correctly classified, and one patient having PD plus ET was classified as PD.ConclusionsBased on the analysis of smartphone accelerometer recordings, we found several kinematic features in the analysis of tremor that distinguished first between healthy subjects and patients and, ultimately, between PD and ET patients. The proposed method can give immediate results for the clinician to gain valuable information for the diagnosis of tremor. This can be useful in environments where more sophisticated diagnostic techniques are unavailable.
| S-EPMC5571972 | biostudies-literature
Project description:Background: Essential tremor (ET) cases often exhibit a range of mild cerebellar signs. Their unaffected relatives have been shown in prior studies to exhibit subtle (i.e., preclinical) disease features. Objective: To quantify subtle cerebellar signs in unaffected first-degree relatives of ET cases stratified based on their tremor severity. Methods: Two hundred sixty-nine first-degree relatives of ET cases, none of whom reported tremor or a diagnosis of ET, or were diagnosed with ET based on detailed neurological examination, were stratified based on total tremor score (TTS) into two groups (lower TTS vs. higher TTS) and quartiles. Changes in gait, balance, and intention tremor were quantified on neurological examination. Results: Higher TTS performed worse on the tandem stance task (p = 0.011). When stratified into TTS quartiles, higher quartile was associated with worse performance in tandem stance (p = 0.011) and stance with feet together (p = 0.028). Similarly, intention tremor in the arms (p = 0.0002) and legs (p = 0.047) were higher in the groups with more tremor. Discussion: The links between ET and the cerebellum are multiple. These data provide intriguing evidence that subtle cerebellar signs (i.e., changes in balance and intention tremor) are more prevalent among first-degree relatives of ET cases with more tremor (i.e., those who may be themselves on the pathway to developing ET). These data contribute to a better characterization of what may be an early subclinical stage of the disease.
| S-EPMC7379149 | biostudies-literature
Project description:BackgroundThe extent of neurodegeneration underlying essential tremor (ET) remains a matter of debate. Despite various extents of cerebellar atrophy on structural magnetic resonance imaging (MRI), previous studies have shown substantial heterogeneity and included a limited number of patients. Novel automated pipelines allow detailed segmentation of cerebellar lobules based on structural MRI.ObjectiveTo compare the volumes of cerebellar lobules in ET patients with those in healthy controls (HCs) using an automated segmentation pipeline.MethodsStructural MRI scans of ET patients eligible for deep brain stimulation (n = 55) and of age-matched and gender-matched HCs (n = 55, from the IXI database) were segmented using the automated CEREbellum Segmentation pipeline. Lobule-specific volume differences between the ET and HC groups were evaluated using a general linear model corrected for multiple tests.ResultsTotal brain tissue volumes did not differ between the ET and HC groups. ET patients demonstrated reduced volumes of lobules I-II, left Crus II, left VIIB, and an increased volume of right X when compared with the HC group.ConclusionA large cohort of ET patients demonstrated subtle signs of decreased cerebellar lobule volumes. These findings oppose the hypothesis of localized atrophy in cerebellar motor areas in ET, but not the possibility of cerebellar pathophysiology in ET. Prospective investigations using alternative neuroimaging modalities may further elucidate the pathophysiology of ET and provide insights into diagnostic and therapeutic approaches.
| S-EPMC8222624 | biostudies-literature
Project description:Surprisingly little has been written about the combined clinical entity, essential tremor-Parkinson's disease (ET-PD), which is the result of a double disease hit. We carefully quantified tremor burden using a wide range of measures (tremor severity, tremor-related disability, tremor-related quality of life) and furthermore, studied additional motor and non-motor features in ET-PD.In this prospective, clinical-epidemiological study, we performed a standardized, structured clinical evaluation of 27 ET-PD patients, comparing them to age-matched samples of 35 PD and 109 ET patients.The number of hours/day shaking was lowest in PD (median=3.0), intermediate in ET (median=10.0) and highest in ET-PD (median=14.0) (p<0.001). All measures of mobility and balance (Berg Balance test, Activities-specific Balance Confidence Scale, Timed Up and Go test) worsened across groups in a stepwise manner from ET to PD to ET-PD (p<0.05). Mini-mental state test scores worsened (p=0.002) and daytime sleepiness increased (p=0.002) across groups from ET to PD to ET-PD.The ET-PD patient seems to be more than just a PD patient with a little more kinetic tremor. Aside from a significantly greater tremor burden, ET-PD patients exhibited more cognitive and sleep problems and more mobility and balance problems than patients with isolated PD.
| S-EPMC5300045 | biostudies-literature
Project description:Although the incidence of ET increases with advancing age, the disease may begin at any age, including childhood. The question arises as to whether childhood-onset ET cases manifest the same sets of pathological changes in the cerebellum as those whose onset is during adult life. We quantified a broad range of postmortem features (Purkinje cell [PC] counts, PC axonal torpedoes, a host of associated axonal changes [PC axonal recurrent collateral count, PC thickened axonal profile count, PC axonal branching count], heterotopic PCs, and basket cell rating) in 60 ET cases (11 childhood-onset and 49 adult-onset) and 30 controls. Compared to controls, childhood-onset ET cases had lower PC counts, higher torpedo counts, higher heterotopic PC counts, higher basket cell plexus rating, and marginally higher PC axonal recurrent collateral counts. The median PC thickened axonal profile count and median PC axonal branching count were two to five times higher in childhood-onset ET than controls, but the differences did not reach statistical significance. Childhood-onset and adult-onset ET had similar PC counts, torpedo counts, heterotopic PC counts, basket cell plexus rating, PC axonal recurrent collateral counts, PC thickened axonal profile count and PC axonal branching count. In conclusion, we found that childhood-onset and adult-onset ET shared similar pathological changes in the cerebellum. The data suggest that pathological changes we have observed in the cerebellum in ET are a part of the pathophysiological cascade of events in both forms of the disease and that both groups seem to reach the same pathological endpoints at a similar age of death.
| S-EPMC5624847 | biostudies-literature
Project description:Genetic polymorphisms in Solute carrier family 1 (glial high affinity glutamate transporter), member 2 (SLC1A2) have been linked with essential tremor. SLC1A2 encodes excitatory amino acid transporter type 2 (EAAT2), which clears glutamate from the synaptic cleft. One postulated mechanism for essential tremor is the over-excitation of glutamatergic olivo-cerebellar climbing fibers, leading to excitotoxic death of Purkinje cells. Other glutamatergic excitatory signals are transmitted to Purkinje cells via parallel fibers of cerebellar granule neurons. Therefore, the expression level of glutamate transporters could be important in essential tremor pathogenesis. Using Western blotting, we compared the expression levels of the two main glutamate transporters in the cerebellar cortex, EAAT1 and EAAT2, in postmortem tissue from 16 essential tremor cases and 13 age-matched controls. We also studied the localization of EAAT1 and EAAT2 using immunohistochemistry in 10 essential tremor cases and 12 controls. EAAT1 protein levels were similar in cases and controls (1.12 ± 0.83 vs. 1.01 ± 0.69, p =0.71) whereas EAAT2 protein levels in essential tremor cases were only 1/3 of that in controls (0.35 ± 0.23 vs. 1.00 ± 0.62, p < 0.01). Interestingly, EAAT2, but not EAAT1, was expressed in astrocytic processes surrounding the Purkinje cell axon initial segment, a region of previously observed pathological changes in essential tremor. Our main finding, a significant reduction in cerebellar cortical EAAT2 protein levels in essential tremor, suggests that Purkinje cells in essential tremor might be more vulnerable to excitotoxic damage than those of controls.
| S-EPMC4239402 | biostudies-literature
Project description:Essential tremor (ET) is one of the most common neurological diseases, with a central feature of an 8-12 Hz kinetic tremor. While previous postmortem studies have identified a cluster of morphological changes in the ET cerebellum centered in/around the Purkinje cell (PC) population, including a loss of PCs in some studies, the underlying molecular mechanisms for these changes are not clear. As genomic studies of ET patients have yet to identify major genetic contributors and animal models that fully recapitulate the human disease do not yet exist, the study of human tissue is currently the most applicable method to gain a mechanistic insight into ET disease pathogenesis. To begin exploration of an underlying molecular source of ET disease pathogenesis, we have performed the first transcriptomic analysis by direct sequencing of RNA from frozen cerebellar cortex tissue in 33 ET patients compared to 21 normal controls. Principal component analysis showed a heterogenous distribution of the expression data in ET patients that only partially overlapped with control patients. Differential expression analysis identified 231 differentially expressed gene transcripts ('top gene hits'), a subset of which has defined expression profiles in the cerebellum across neuronal and glial cell types but a largely unknown relationship to cerebellar function and/or ET pathogenesis. Gene set enrichment analysis (GSEA) identified dysregulated pathways of interest and stratified dysregulation among ET cases. By GSEA and mining curated databases, we compiled major categories of dysregulated processes and clustered string networks of known interacting proteins. Here we demonstrate that these 'top gene hits' contribute to regulation of four main biological processes, which are 1) axon guidance, 2) microtubule motor activity, 3) endoplasmic reticulum (ER) to Golgi transport and 4) calcium signaling/synaptic transmission. The results of our transcriptomic analysis suggest there is a range of different processes involved among ET cases, and draws attention to a particular set of genes and regulatory pathways that provide an initial platform to further explore the underlying biology of ET.
| S-EPMC7593093 | biostudies-literature