Ataxia Prevalence in Primary Orthostatic Tremor.

Background: The exact pathophysiology of primary Orthostatic Tremor (OT) is unknown. A central oscillator is assumed, and previous imaging studies show involvement of cerebellar pathways. However, the presence of ataxia on clinical exam is disputed. We set out to study ataxia in OT prospectively. Methods: EMG-confirmed primary OT subjects and spousal controls received a neurological exam with additional semiquantitative evaluations of ataxia as part of a multinational, prospective study. These included detailed limb coordination (DLC), detailed stance and gait evaluation (DS), and the Brief Ataxia Rating Scale (BARS). Intra- and inter-rater reliability were assessed and satisfactory. Results: 34 OT subjects (mean age = 67 years, 88% female) and 21 controls (mean age = 66 years, 65% male) were enrolled. Average disease duration was 18 years (range 4-44). BARS items were abnormal in 88% of OT patients. The OT subjects were more likely to have appendicular and truncal ataxia with significant differences in DLC, DS and BARS. Ocular ataxia and dysarthria were not statistically different between the groups. Discussion: Mild-to-moderate ataxia could be more common in OT than previously thought. This is supportive of cerebellar involvement in the pathophysiology of OT. We discuss possible implications for clinical care and future research. Highlights: Previous studies of Primary Orthostatic Tremor (OT) have proposed pathophysiologic involvement of the cerebellar pathways.However, presence of ataxia has not been systematically studied in OT.This is a prospective comprehensive ataxia assessment in OT compared to controls. Mild-to-moderate appendiculo-truncal ataxia was found to be common in OT.

Molecular mechanisms of long noncoding RNAs and their role in disease pathogenesis.

LncRNAs are long non-coding regulatory RNAs that are longer than 200 nucleotides. One of the major functions of lncRNAs is the regulation of specific gene expression at multiple steps including, recruitment and expression of basal transcription machinery, post-transcriptional modifications and epigenetics [1]. Emerging evidence suggests that lncRNAs also play a critical role in maintaining tissue homeostasis during physiological and pathological conditions, lipid homeostasis, as well as epithelial and smooth muscle cell homeostasis, a topic that has been elegantly reviewed [2-5]. While aberrant expression of lncRNAs has been implicated in several disease conditions, there is paucity of information about their contribution to the etiology of diseases [6]. Several studies have compared the expression of lncRNAs under normal and cancerous conditions and found differential expression of several lncRNAs, suggesting thereby an involvement of lncRNAs in disease processes [7, 8]. Furthermore, the ability of lncRNAs to influence epigenetic changes also underlies their role in disease pathogenesis since epigenetic regulation is known to play a critical role in many human diseases [1]. LncRNAs thus are not only involved in homeostatic functioning but also play a vital role in the progression of many diseases, thereby underscoring their potential as novel therapeutic targets for the alleviation of a variety of human disease conditions.