Evaluating Mild Cognitive Impairment in Essential Tremor: How Many and Which Neuropsychological Tests?

OBJECTIVES: Essential tremor (ET) confers an increased risk for developing both amnestic and non-amnestic mild cognitive impairment (MCI). Yet, the optimal measures for detecting mild cognitive changes in individuals with this movement disorder have not been established. We sought to identify the cognitive domains and specific motor-free neuropsychological tests that are most sensitive to mild deficits in cognition as defined by a Clinical Dementia Rating (CDR) of 0.5, which is generally associated with a clinical diagnosis of MCI. METHODS: A total of 196 ET subjects enrolled in a prospective, longitudinal, clinical-pathological study underwent an extensive motor-free neuropsychological test battery and were assigned a CDR score. Logistic regression analyses were performed to identify the neuropsychological tests which best identified individuals with CDR of 0.5 (mild deficits in cognition) versus 0 (normal cognition). RESULTS: In regression models, we identified five tests in the domains of Memory and Executive Function which best discriminated subjects with CDR of 0.5 versus 0 (86.9% model classification accuracy). These tests were the California Verbal Learning Test II Total Recall, Logical Memory II, Verbal-Paired Associates I, Category Switching Fluency, and Color-Word Inhibition. CONCLUSIONS: Mild cognitive difficulty among ET subjects is best predicted by combined performance on five measures of memory and executive function. These results inform the nature of cognitive dysfunction in ET and the creation of a brief cognitive battery to assess patients with ET for cognitively driven dysfunction in life that could indicate the presence of MCI. (JINS, 2018, 24, 1084-1098).

The effect of MAPT haplotype on neocortical Lewy body pathology in Parkinson disease.

The H1 haplotype of the microtubule-associated protein tau gene (MAPT) is associated with an increased risk of Parkinson disease (PD) compared with the H2 haplotype, but its effect on Lewy body (LB) formation is unclear. In this study, we compared the MAPT haplotype frequency between pathologically confirmed PD patients (n = 71) and controls (n = 52). We analyzed Braak LB stage, Braak neurofibrillary tangle (NFT) stage, and CERAD amyloid score by haplotype. We further tested the association between MAPT haplotype and semi-quantitative counts of LBs, NFTs, and neuritic plaques (NPs) in multiple neocortical regions. Consistent with previous reports, PD cases had an increased likelihood of carrying an H1/H1 genotype compared to controls (OR = 5.72, 95 % CI 1.80-18.21, p = 0.003). Braak LB, Braak NFT and CERAD scores did not differ by haplotype. However, H1/H1 carriers had higher LB counts in parietal cortex (p = 0.02) and in overall neocortical LBs (p = 0.03) compared to non-H1/H1 cases. Our analyses suggest that PD patients homozygous for the H1 haplotype have a higher burden of neocortical LB pathology.

Black and hispanic patients with movement disorders less likely to undergo deep brain stimulation.

BACKGROUND: DBS is an effective surgical treatment for ET, PD, and dystonia. Racial disparities in DBS utilization in PD have been documented demonstrating that Black patients receive DBS at lower rates than White patients. To our knowledge, no studies have investigated if this pattern of non-use persists in other movement disorders with FDA-approval. OBJECTIVE: To identify racial and ethnic disparities in DBS utilization in those hospitalized for ET, PD, and dystonia. METHODS: The NIS database was queried for US hospitalizations from 2012 to 2018 with a primary diagnosis of ET, PD, or dystonia, and a total of 3,363, 21,963, and 1,835 discharges were recorded, respectively. Within that sample, treatment with DBS was identified. Sex, race, age, payment method, income quartile, year, mortality risk, hospital size, urban/rural setting, teaching status, and geographic region were extracted. A multivariate logistic regression was performed to identify predictors for use and non-use of DBS. RESULTS: Between 2012 and 2018, Black patients with PD, ET, and dystonia were less likely to receive DBS than White patients. Black patients with PD were 7 times less likely to receive DBS (OR = 0.145, CI = 0.111-0.189), and Black patients with ET and dystonia were 5 times less likely to receive DBS than White patients (OR = 0.188, CI = 0.124-0.285; OR = 0.186, CI = 0.084-0.414). Compared to White patients, Hispanic patients with PD (OR = 0.631, OR = 0.539-0.740) and ET (OR = 0.438, CI = 0.277-0.695) were less likely to undergo DBS. When controlling for patient and hospital level characteristics, racial and ethnic disparities remained. CONCLUSIONS: Our data suggest that Black patients with a diagnosis of ET, PD, or dystonia and Hispanic patients with a diagnosis of ET or PD were less likely to be treated with DBS than White patients between 2012 and 2018.

Structural and functional brain changes in hepatic and neurological Wilson disease.

Wilson disease (WD) can manifest with hepatic or neuropsychiatric symptoms. Our understanding of the in vivo brain changes in WD, particularly in the hepatic phenotype, is limited. Thirty subjects with WD and 30 age- and gender-matched controls participated. WD group underwent neuropsychiatric assessment. Unified WD Rating Scale neurological exam scores were used to determine neurological (WDN, score > 0) and hepatic-only (WDH, score 0) subgroups. All subjects underwent 3 Tesla anatomical and resting-state functional MRI. Diffusion tensor imaging (DTI) and susceptibility-weighted imaging (SWI) were performed only in the WD group. Volumetric, DTI, and functional connectivity analyses were performed to determine between-group differences. WDN and WDH groups were matched in demographic and psychiatric profiles. The entire WD group compared to controls showed significant thinning in the bilateral superior frontal cortex. The WDN group compared to control and WDH groups showed prominent structural brain changes including significant striatal and thalamic atrophy, more subcortical hypointense lesions on SWI, and diminished white matter integrity in the bilateral anterior corona radiata and corpus callosum. However, the WDH group also showed significant white matter volume loss compared to controls. The functional connectivity between the frontostriatal nodes was significantly reduced in the WDN group, whereas that of the hippocampus was significantly increased in the WDH group compared to controls. In summary, structural and functional brain changes were present even in neurologically non-manifesting WD patients in this cross-sectional study. Longitudinal brain MRI scans may be useful as biomarkers for prognostication and optimization of treatment strategies in WD.

How Much Do We Know about Adult-onset Primary Tics? Prevalence, Epidemiology, and Clinical Features.

BACKGROUND: Tic disorders are generally considered to be of pediatric onset; however, reports of adult-onset tics exist in the literature. Tics can be categorized as either primary or secondary, with the latter being the larger group in adults. Primary or idiopathic tics that arise in adulthood make up a subset of tic disorders whose epidemiologic and clinical features have not been well delineated. METHODS: Articles to be included in this review were identified by searching PubMed, SCOPUS, and Web of Science using the terms adult- and late-onset tics, which resulted in 120 unique articles. Duplicates were removed. Citing references were identified using Google Scholar; all references were reviewed for relevance. RESULTS: The epidemiologic characteristics, clinical phenomenology, and optimal treatment of adult-onset tics have not been ascertained. Twenty-six patients with adult-onset, primary tics were identified from prior case reports. The frequency of psychiatric comorbidities may be lower in adults than in children, and obsessive compulsive disorder was the most common comorbidity. Adult-onset primary tics tend to wax and wane, occur predominantly in males, are often both motor and phonic in the same individual, and are characterized by a poor response to treatment. DISCUSSION: We know little about adult-onset tic disorders, particularly ones without a secondary association or cause. They are not common, and from the limited data available, appear to share some but not all features with childhood tics. Further research will be important in gaining a better understanding of the epidemiology and clinical manifestations of this disorder.

Tic Exacerbation in Adults with Tourette Syndrome: A Case Series.

BACKGROUND: Tourette syndrome (TS) has been described as peaking in adolescence with subsequent regression. We report patients who were diagnosed with TS during childhood who experienced a latent period (significant reduction in or absence of tics) followed by tic re-emergence in adulthood. METHODS: We performed a retrospective chart review of outpatients over age 21 seen at the Yale neurology clinic between January 2012 and July 2016 who were diagnosed with childhood-onset tics, and who experienced a latent period of greater than 1 year followed by an exacerbation. RESULTS: Sixteen patients were identified. The mean latent period was 16 years. Ten patients (62.5%) identified an exacerbation trigger, most commonly changes in substance use (five patients). Seven patients (43.8%) reported worsening of tics since childhood. Six patients (37.5%) had received pharmacological intervention for tics as children, and 15 patients (93.8%) as adults. Six of 15 patients (40.0%) had an effective response from those pharmacological intervention(s). DISCUSSION: Our study demonstrates that the decline in symptoms as patients age may represent temporary improvement. The latent period lasted years in our patients, different from the more rapid waxing and waning in children. A change in substance use was an important trigger. Requests for pharmacological intervention were not necessarily correlated with worsening tic severity.

Head tremor in essential tremor: "Yes-yes", "no-no", or "round and round"?

INTRODUCTION: Essential tremor (ET) is a common yet frequently misdiagnosed movement disorder. One contributing factor may be the dearth of studies that focus on the nuances of clinical phenomenology. A clinical feature that has received relatively little attention is head tremor. Indeed, there is no consensus regarding the predominant direction of head tremor in ET, and no study has examined the clinical correlates of directionality. METHODS: We identified 51 ET cases with head tremor enrolled in a clinical-epidemiological study of ET at Columbia University. Each had a videotaped neurological examination. Videotapes were viewed and coded by a movement disorders neurologist for head tremor direction ("no-no", "yes-yes", or mixed) and continuity (continuous, intermittent, or rare). Direction was correlated with a wide range of clinical features. RESULTS: Fourteen cases (27.5%) had "no-no" tremor, 9 (17.6%) had "yes-yes" tremor, and 28 (54.9%) had a mixed tremor. Mixed and "yes-yes" cases were older (p = 0.004) and had a longer tremor duration (p = 0.018) than "no-no" cases. Tremor severity (arms) was higher for mixed cases than for "yes-yes" and "no-no" cases (p = 0.04). More mixed cases had continuously present tremor while more "no-no" cases had rare head tremor (p < 0.001). CONCLUSIONS: Head tremor in ET seems to start as an infrequent tremor in one direction (esp. "no-no") and becomes more frequent while acquiring additional directionality and a mixed phenotype as the disease progresses. These findings add to our understanding of the clinical spectrum of ET.

Self-reported physical activity in essential tremor: Relationship with tremor, balance, and cognitive function.

BACKGROUND: Physical inactivity may be the result of medical comorbidities. Inactivity itself may also lead to important health consequences, especially in older patients. Essential tremor (ET) patients may have a variety of physical and cognitive problems that could detrimentally impact on level of physical activity. Yet, to our knowledge, there have been no studies of physical activity in these patients. METHODS: Self-reported physical activity was assessed using the Physical Activity Scale for the Elderly (PASE) in 100 ET cases (mean age 80.5years) enrolled in a clinical study. Additional clinical measures were the total tremor score, Montreal Cognitive Assessment (MOCA) score and number of steps taken off of the straight line during tandem gait (a measure of balance). RESULTS: Lower PASE score was associated with older age, more tandem gait difficulty, higher total tremor score and lower MOCA score (all p<0.05). In a linear regression model that included total tremor score, MOCA score, number of steps off of the straight line during tandem gait, and age, higher total tremor score (p=0.046) and more steps off of the straight line during tandem gait (p=0.014) were independently associated with reductions in physical activity. CONCLUSIONS: Several of the motor features of ET (tremor and imbalance) are independently associated with reductions in level of physical activity.

Public Knowledge and Attitude toward Essential Tremor: A Questionnaire Survey.

BACKGROUND: Public awareness of and attitude toward disease is an important issue for patients. Public awareness of essential tremor (ET) has never been studied. METHODS: We administered a 10-min, 31-item questionnaire to 250 consecutive enrollees. These included three samples carefully chosen to have a potential range of awareness of ET: 100 individuals ascertained from a vascular disease clinic, 100 individuals from a general neurology clinic, and 50 Parkinson's disease (PD) patients. RESULTS: Leaving aside PD patients, only 10-15% of enrollees had ever heard of or read about "ET." Even among PD patients, only 32.7% had ever heard of or read about ET. After providing enrollees with three synonymous terms for ET ("benign tremor," "kinetic tremor," "familial tremor"), ~40% of non-PD enrollees and 51.0% with PD had ever heard or read about the condition. Even among participants who had heard of ET, ~10% did not know what the main symptom was, 1/3 were either unsure or thought ET was the same disease as PD, 1/4 thought that ET was the same condition as frailty- or aging-associated tremor, 2/3 attributed it to odd causes (e.g., trauma or alcohol abuse), only 1/3 knew of the existence of therapeutic brain surgery, fewer than 1/2 knew that children could have ET, and 3/4 did not know of a celebrity or historical figure with ET. Hence, lack of knowledge and misconceptions were common. CONCLUSION: Public knowledge of the existence and features of ET is overall poor. Greater awareness is important for the ET community.

Defining the Role of the Monoamine Oxidase-B Inhibitors for Parkinson's Disease.

Inhibitors of monoamine oxidase-B (MAO-B) occupy an important place in the treatment of Parkinson's disease. Selegiline was the first MAO-B to be used therapeutically, while rasagiline is a second-generation drug with higher potency and selectivity. Safinamide is an investigational MAO-B inhibitor with non-dopaminergic properties that may provide advantages over its predecessors. As a class, MAO-B inhibitors are safe and well tolerated and provide symptomatic benefit both as monotherapy and in combination with other antiparkinsonian medications from early to late stages of disease. In combination with levodopa, MAO-B inhibitors may improve motor fluctuations and allow for lower total doses of levodopa. Patient characteristics and preferences can be important factors in deciding between agents. As a class, MAO-B inhibitors have shown promise as disease-modifying agents, but the clinical trial evidence to date has not been strong enough to afford them such a label. Future research may help further elucidate their relative merits and clarify their role in altering disease progression.

Another case of "shopping bag" tremor: a difficult to classify action tremor.

This letter was written in response to: Zesiewicz T, Vu T, Carranza MA, et al. Unusual wrist tremor: unilateral isometric tremor? Tremor Other Hyperkinet Mov. 2014; 4: http://tremorjournal.org/article/view/194.