Background: Cognitive impairment is a feature of essential tremor (ET). There are no studies of the genetic drivers of this association. We examined whether the microtubule-associated protein tau (MAPT) H1 haplotype is associated with cognitive performance in ET. Methods: ET cases genotyped for the MAPT H1 and H2 haplotypes completed a battery of neuropsychological tests at baseline and four follow-up evaluations. Chi-square, t-tests, and analyses of covariance examined associations between the presence of the MAPT H1 haplotype, cognitive diagnoses of normal, mild cognitive impairment (MCI), and dementia, and performance in specific cognitive domains. Results: We observed no evidence of cognitive differences as a function of the presence of the MAPT H1 haplotype. Specifically, cases with (n = 57) and without (n = 42) this haplotype did not differ with respect to the prevalence of diagnoses of MCI or dementia, p ≥ 0.87. Moreover, cases with vs without this haplotype did not differ in either the age or point in the disease course at which observed conversions to MCI or dementia occurred, p’s ≥ 0.51. Finally, no haplotype-related differences were observed in performance in the cognitive domains of attention, executive function, language, memory, visuospatial or global ability, p’s ≥ 0.21, or in changes in performance in these domains across time, p’s ≥ 0.08. Discussion: The study in an ET cohort revealed no influence of MAPT haplotypes on cognitive performance. This study serves as a valuable foundation for future studies to expand our understanding of the genetic drivers of cognitive impairment in ET. Highlights This study found no evidence of cognitive differences between individuals with and without the MAPT H1 haplotype. Our work provides a valuable foundation for future work to expand our knowledge of the genetic drivers of cognitive impairment in ET.

/pdf/cognitive-performance-as-a-function-of-mapt-haplotype-a-3azaulxk.pdf

Cognitive Performance as a Function of MAPT Haplotype: A Prospective Longitudinal Study of an Essential Tremor Cohort

Non-motor symptoms, including depression and cognitive impairment, are common in essential tremor (ET), but associations between these symptoms and tremor are poorly understood.A retrospective, single-institution, cohort study evaluated 140 patients with ET undergoing evaluation for deep brain stimulation (DBS) surgery. The Fahn-Tolosa-Marin (FTM) or Washington Heights-Inwood Genetic Study of ET (WHIGET) scale was used to grade tremor. Tremor scores were divided into quartiles. Patients underwent clinical neuropsychological evaluations that included a comprehensive cognitive test battery and Beck Depression Inventory-II (BDI-II). Subgroup analysis was performed with groups who met criteria for depression (BDI-II > 14) or overall cognitive impairment (<9th percentile on at least two dissimilar cognitive tests). Independent samples t-tests were used for continuous variables and chi square tests for categorical variables. Univariable and multivariable regressions were used to determine relationships between tremor and non-motor scores.Tremor quartile was correlated with language domain performance (p = 0.044) but not depression scores. FTM score was associated with BDI-II (β = 0.940, p = 0.010), language (β = -0.936, p = 0.012), and visuospatial domain (β = -0.836, p = 0.025) scores, such that worse tremor was associated with more depression and worse language and visuospatial function. WHIGET score was not associated with any neuropsychological scores on multivariable regression.FTM score was associated with language, visuospatial, and mood symptoms, suggesting a relationship between the severity of these symptom types. Different tremor scores capture different motor symptoms and relationships with nonmotor symptoms. 

The association between motor and non-motor symptoms in essential tremor patients being evaluated for deep brain stimulation surgery

Most of the antiseizure medications (ASMs) are metabolized in liver and many of them particularly first-generation ASMs have the potential to increase liver enzymes or induce liver injury. Hence, treatment of new onset seizures or epilepsy by ASMs during the course of coronavirus disease 2019 (COVID-19), which could potentially be complicated by hepatic dysfunction, is a challenging clinical issue. Intravenous form of levetiracetam which has no significant hepatic metabolism or drug-drug interaction is often a favorable option to control seizures in acute phase of COVID-19. Administration of enzyme inducer ASMs and valproate with the well-known hepatotoxicity and common drug interactions is not generally recommended. In patients with epilepsy who are under control with potentially hepatotoxic ASMs, close observation and cautious dose reduction or drug switch should be considered if any evidence of hepatic impairment exists. However, risks of possible breakthrough seizures should be weighed against benefits of lowering the hazard of liver injury. In patients with epilepsy who receive polytherapy with ASMs, transient dose modification with the tendency to increase the dose of ASMs with more favorable safety profile and less drug interaction and decrease the dose of drugs with main hepatic metabolism, high protein binding, potential to cause liver injury and known drug-drug reaction should be considered. Finally, decision making should be individualized based on patients’ conditions and course of illness.

Potential risk of liver injury in epileptic patients during COVID-19 pandemic

Introduction: Essential tremor (ET) is one of the most common movement disorders. Oral drugs play a crucial role in treating ET, with various available options such as propranolol, primidone, and topiramate. However, the medication status and related factors among Chinese ET patients are unknown yet. Methods: This study used the baseline data from the National Survey of Essential Tremor Plus in China cohort. ET patients with information related to medication intake were included. Medication patients were defined as patients who were taking medication at the time of the survey. We further defined recommended medication users according to Chinese guideline recommendations and clinical knowledge. We used mean and standard deviation (SD), median and interquartile range (IQR), or frequencies and percentages when appropriate for descriptive analysis. We used multivariate logistic regression analyses to explore factors related to medication intake in all ET patients and in recommended medication users. Results: Of 1,153 included ET participants, 207 (18.0%) took medication. Arotinolol (115, 55.6%) and propranolol (63, 30.4%) were the top 2 used medicines. Patients with middle school education (odds ratio 0.57, 95% confidence interval 0.39–0.83), college or higher level education (0.46, 0.28–0.76), and late-onset ET (LO-ET) (0.38, 0.23–0.63) were less likely to take medication. Patients with intention tremor (1.90, 1.38–2.62), every 10-unit increase in age (1.10, 1.00–1.21), Tremor Research Group Essential Tremor Rating Assessment Scale (TETRAS) Part 1 (1.63, 1.37–1.93), and TETRAS Part 2 (1.81, 1.48–2.22) were more likely to take medication. Among 332 recommended medication users, only 104 (31.3%) took medicine. The associations of LO-ET (0.36, 0.17–0.75), intention tremor (2.27, 1.35–3.81), TETRAS Part 1 (1.52, 1.09–2.13), and TETRAS Part 2 (1.59, 1.15–2.20) with medication were similar to all ET patients. Conclusion: The proportion of medication intake is low among both all ET patients and recommended medication users. The top 2 commonly used medications among all ET patients are arotinolol and propranolol. Influencing factors of medication intake are different between all ET patients and recommended medication users. Clinicians are suggested to provide counseling and education on ET medication to promote medication intake.

Medication Status and Related Factors in Essential Tremor Patients: A Cross-Sectional Study in China

Background: Although managing symptoms is paramount for both essential tremor (ET) patients and their healthcare providers, studies of treatment satisfaction are surprisingly lacking. Objectives: We evaluated the satisfaction of patients who used a range of treatments and assessed the relation of a wide array of factors to satisfaction. Methods: One hundred four ET participants (age = 74.5 ± 10.2 years) completed a battery of self-report items. These included demographic information, measures of tremor and clinical history, psychological state, current ET treatment, and a series of questions about satisfaction with treatment. Results: Analyses of responses to the four current treatment satisfaction questions revealed that the proportion of participants who were satisfied ranged from 35.0% to 57.3% (i.e., approximately 1/3 to 1/2); conversely, the proportion who were dissatisfied ranged from 9.2% to 37.0%. The remainder were neutral. Higher satisfaction levels were observed in participants who were included in treatment selection and who had undergone deep brain stimulation surgery, p’s &lt; 0.05. Lower levels of satisfaction were found in participants with a negative psychological state, higher self-rated tremor severity, head/voice/jaw tremors, and more severe physical side effects; and who used botulinum toxin therapy, p’s &lt; 0.05. Conclusion: Between 1/3 and 1/2 of patients were satisfied with their treatment, whereas up to 1/3 were dissatisfied. In this initial exploration of correlates of treatment satisfaction in ET patients, we identified a number of associations between satisfaction and clinical, psychological and treatment variables. Additional research is warranted to further explore the nature of these relations over time. 

Patient-reported treatment satisfaction in essential tremor: levels of satisfaction and predictors of satisfaction

Prospective, longitudinal analysis of medication use in a cohort of elderly essential tremor cases

Depressive symptoms predict memory decline in Essential Tremor.

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Prospective, longitudinal analysis of medication use in a cohort of elderly essential tremor cases

Depressive symptoms predict memory decline in Essential Tremor.