Background Consensus criteria for classifying tremor disorders were published by the International Parkinson and Movement Disorder Society in 1998. Subsequent advances with regard to essential tremor, tremor associated with dystonia, and other monosymptomatic and indeterminate tremors make a significant revision necessary. Objectives Convene an international panel of experienced investigators to review the definition and classification of tremor. Methods Computerized MEDLINE searches in January 2013 and 2015 were conducted using a combination of text words and MeSH terms: “tremor”, “tremor disorders”, “essential tremor”, “dystonic tremor”, and “classification” limited to human studies. Agreement was obtained using consensus development methodology during four in‐person meetings, two teleconferences, and numerous manuscript reviews. Results Tremor is defined as an involuntary, rhythmic, oscillatory movement of a body part and is classified along two axes: Axis 1—clinical characteristics, including historical features (age at onset, family history, and temporal evolution), tremor characteristics (body distribution, activation condition), associated signs (systemic, neurological), and laboratory tests (electrophysiology, imaging); and Axis 2—etiology (acquired, genetic, or idiopathic). Tremor syndromes, consisting of either isolated tremor or tremor combined with other clinical features, are defined within Axis 1. This classification scheme retains the currently accepted tremor syndromes, including essential tremor, and provides a framework for defining new syndromes. Conclusions This approach should be particularly useful in elucidating isolated tremor syndromes and syndromes consisting of tremor and other signs of uncertain significance. Consistently defined Axis 1 syndromes are needed to facilitate the elucidation of specific etiologies in Axis 2. © 2017 International Parkinson and Movement Disorder Society

Despite its being one of the most commonly observed neurological disorders, neuropathological studies of essential tremor (ET) are rare. There have been surprisingly few autopsy studies and even fewer case-control comparisons. The primary objective was to describe and quantify the pathological changes in 33 ET and 21 control brains. A secondary objective was to correlate clinical and pathological features. We examined autopsy tissue from the Essential Tremor Centralized Brain Repository. Eight (24.2%) of the 33 ET brains had Lewy bodies in the brainstem, mainly in the locus ceruleus. However, the majority of ET brains (25/33, 75.8%) had no Lewy bodies, but had pathological changes in the cerebellum. The mean number of Purkinje cells per 100x field was reduced in ET cases without Lewy bodies (6.6 +/- 2.4 versus 9.6 +/- 3.4, P < 0.01), and there were approximately 7x more Purkinje cell torpedoes per section (12.6 +/- 7.9 versus 1.7 +/- 1.4, P < 0.001) compared to controls. ET cases without Lewy bodies also had degeneration of the dentate nucleus (two cases). Other findings in ET cases were Purkinje cell heterotopias and dendrite swellings. Lewy body ET cases were older than ET cases without Lewy bodies. Several trends were observed in ET cases without Lewy bodies, including a younger age of onset of tremor and higher proportions with gait difficulty and family history of ET. The pathological changes of ET seem to be heterogeneous and degenerative. The majority have cerebellar changes without Lewy bodies; a smaller proportion has brainstem Lewy bodies. The clinical differences between cases with versus without Lewy bodies require additional study.

Fragile X-associated Tremor Ataxia Syndrome (FXTAS) results from a CGG repeat expansion in the 5’UTR of FMR1. This repeat is thought to elicit toxicity as RNA yet disease brains contain ubiquitin-positive neuronal inclusions, a pathologic hallmark of protein-mediated neurodegeneration. We explain this paradox by demonstrating that CGG repeats trigger repeat associated non-AUG initiated (RAN) translation of a cryptic polyglycine-containing protein, FMRpolyG. FMRpolyG accumulates in ubiquitin-positive inclusions in Drosophila, cell culture, mouse disease models and FXTAS patient brains. CGG RAN translation occurs in at least two of three possible reading frames at repeat sizes ranging from normal (25) to pathogenic (90), but inclusion formation only occurs with expanded repeats. In Drosophila, CGG repeat toxicity is suppressed by eliminating RAN translation and enhanced by increased polyglycine protein production. These studies expand the growing list of nucleotide repeat disorders where RAN translation occurs and provide evidence that RAN translation contributes to neurodegeneration.

Essential tremor (ET) is among the more prevalent neurological disorders, yet prevalence estimates have varied enormously, making it difficult to establish prevalence with precision. We: (1) reviewed the worldwide prevalence of ET in population-based epidemiological studies, (2) derived as precisely as possible an estimate of disease prevalence, and (3) examined trends and important differences across studies. We identified 28 population-based prevalence studies (19 countries). In a meta-analysis, pooled prevalence (all ages) = 0.9%, with statistically significant heterogeneity across studies (I(2) = 99%, P < 0.001). In additional descriptive analyses, crude prevalence (all ages) = 0.4%. Prevalence increased markedly with age, and especially with advanced age. In the meta-analysis, prevalence (age >or= 65 years) = 4.6%, and in additional descriptive analyses, median crude prevalence (age >or= 60-65) = 6.3%. In one study of those age >or= 95 years, crude prevalence = 21.7%. Several studies reported ethnic differences in prevalence, although more studies are needed. Greater than one-third of studies show a gender difference, with most demonstrating a higher prevalence among men. This possible gender preference is interesting given clinical, epidemiological, and pathological associations between ET and Parkinson's disease. Precise prevalence estimates such as those we provide are important because they form the numerical basis for planned public health initiatives, provide data on the background occurrence of disease for family studies, and offer clues about the existence of environmental or underlying biological factors of possible mechanistic importance.

The Unified Huntington's Disease Rating Scale (UHDRS) was developed as a clinical rating scale to assess four domains of clinical performance and capacity in HD: motor function, cognitive function, behavioral abnormalities, and functional capacity. We assessed the internal consistency and the intercorrelations for the four domains and examined changes in ratings over time. We also performed an interrater reliability study of the motor assessment. We found there was a high degree of internal consistency within each of the domains of the UHDRS and that there were significant intercorrelations between the domains of the UHDRS, with the exception of the total behavioral score. There was an excellent degree of interrater reliability for the motor scores. Our limited longitudinal database indicates that the UHDRS may be useful for tracking changes in the clinical features of HD over time. The UHDRS assesses relevant clinical features of HD and appears to be appropriate for repeated administration during clinical studies.

Objective: To determine the predictive utility of baseline odor identification deficits for future cognitive decline and the diagnosis of Alzheimer disease (AD) dementia.Methods: In a multiethnic community cohort in North Manhattan, NY, 1,037 participants without dementia were evaluated with the 40-item University of Pennsylvania Smell Identification Test (UPSIT). In 757 participants, follow-up occurred at 2 years and 4 years.Results: In logistic regression analyses, lower baseline UPSIT scores were associated with cognitive decline (relative risk 1.067 per point interval; 95% confidence interval [CI] 1.040, 1.095; p , 0.0001), and remained significant (relative risk 1.065 per point interval; 95% CI 1.034, 1.095; p , 0.0001) after including covariates. UPSIT, but not Selective Reminding Test-total immediate recall, predicted cognitive decline in participants without baseline cognitive impairment. During follow-up, 101 participants transitioned to AD dementia. In discrete time survival analyses, lower baseline UPSIT scores were associated with transition to AD dementia (hazard ratio 1.099 per point interval; 95% CI 1.067, 1.131; p , 0.0001), and remained highly significant (hazard ratio 1.072 per point interval; 95% CI 1.036, 1.109; p , 0.0001) after including demographic, cognitive, and functional covariates.Conclusions: Impairment in odor identification was superior to deficits in verbal episodic memory in predicting cognitive decline in cognitively intact participants. The findings support the crosscultural use of a relatively inexpensive odor identification test as an early biomarker of cognitive decline and AD dementia. Such testing may have the potential to select/stratify patients in treatment trials of cognitively impaired patients or prevention trials in cognitively intact individuals.Neurology ® 2015;84:182-189 GLOSSARY AD 5 Alzheimer disease; AUC 5 area under the curve; CI 5 confidence interval; HR 5 hazard ratio; MCI 5 mild cognitive impairment; ROC 5 receiver operating characteristic; RR 5 relative risk; SRT 5 Selective Reminding Test; SRT-TR 5 Selective Reminding Test-total immediate recall; UPSIT 5 University of Pennsylvania Smell Identification Test; WHICAP 5 Washington Heights/Inwood Columbia Aging Project.

Essential tremor (ET) is the most common adult movement disorder, as much as 20 times more prevalent than Parkinson's disease. Estimates of the crude prevalence of ET range widely from 0.08 to 220 cases per 1000 persons, a 2750-fold difference. There has been no formal attempt to synthesize these disparate results. Our purpose is to provide an overview of existing studies, to examine methodologic issues that may account for this tremendous variability in results, and to provide a more precise estimate of the prevalence of ET. Nineteen studies of the prevalence of ET were reviewed. Factors that contribute to the broad range of prevalence estimates include (a) differences in study design that influence validity and (b) differences in characteristics of study populations that influence comparability of studies. If we limit our examination to studies that (a) provided diagnostic criteria for ET, (b) defined ET as an action tremor, and (c) used community-based rather than service-based designs, then five studies remain, and the prevalence of ET is 4.1 to 39.2 cases per 1000, a 9.6-fold difference. Four of these five provided age-stratified data. Among these four, the prevalence of ET in those over the age of 60 years was 13.0 to 50.5 cases per 1000, a 3.9-fold difference.

Estimates of the prevalence of essential tremor (ET) are probably low because screening questionnaires have been used. The authors estimated the prevalence of ET in Mersin Province, Turkey, in 2,253 individuals aged >or=40 years, all of whom were examined by study neurologists. There were 89 ET cases (prevalence = 4.0%, 95% CI = 3.2 to 4.8%). The prevalence of ET may be higher than previously estimated. This is important when defining the extent of the health care problem.