Identifying Markers of Disease Subtypes and Disease Progression in the Syndrome of Essential Tremor

Determine the prevalence of ET-plus within a prospectively collected ET population

age at disease onset and age at baseline

male, female, other

positive or negative for essential tremor or Parkinson's disease

e.g. rest tremor, impaired tandem gait, mild parkinsonian signs, questionable dystonia, mild cognitive impairment

e.g. propranolol yes vs no, topiramate yes vs no, primidone yes vs no

no progression, slowly and continuously, relapsing, plateau-like after initial progression, rapidly progressive

amelioration of tremor severity after consumption of alcohol (yes vs. no vs. unknown)

arterial hypertension yes vs. no, hyperlipidemia yes vs. no, smoking yes vs. no vs. former, diabetes mellitus yes vs. no, coronary artery disease yes vs. no

rates clinical severity of parkinsonian symptoms, range 0-260 points with higher points meaning more severe symptoms

rates clinical severity of ET symptoms, ranging from 0-80 (the "modified" means the inclusion of 2 additional items rating rest tremor) with higher points meaning more severe motor symptoms; also includes a subscale rating activities of daily living ranging from 0-48 points with more points meaning more severe disability due to ET

assesses symptoms of ataxia, ranging from 0 (no ataxia) to 40 (most severe ataxia)

patients needs to say as many animals as possible within 1 minute, the more, the better

the patient needs to name 15 items (shown as pictures) correctly, the more, the better

a cognitive screening test with a minimum of 0 and a maximum of 30 points

the patient is shown 10 words which he needs to remember and repeat immediately after reading them (within 90 seconds); there a three tries; the more he remembers, the better

the patient needs to draw 4 figures from a model which are then rated according to prespecified criteria (maximum of 11 points, the more the better)

the patient needs to remember as many of the 10 words learned in "word list learning"; time limit 90 seconds

the patient needs decide whether a word shown to him was part of the 10 words learned before; there a 20 words in total, and 10 each were part of the learned words while 10 where not; the more he/she remembers correctly, the better (1 point for each correctly identified word)

the patients needs to draw the 4 figures from "constructive praxis" from memory; they are then rated according to the same criteria with a maximum of 11 points

the patient needs to connect numbers in ascending order from 1 to 25, time is measured in seconds (the faster, the better)

the patient needs to connect numbers and letters in ascending and alternating order from 1 to 13 and A to L, respectively, time is measured in seconds (the faster, the better)

the patient needs to list as many words starting with the letter "s" within 60 seconds as possible; the more the better

a neuropsychological test focusing on executive function, ranging from 0 (most impaired) to 18 (normal)

a short questionnaire rating depressive symptoms, ranging from 0 (no depressive symptoms) to 15 (most severe depressive symptoms)

a questionnaire rating anxiety and depressive symptoms, ranging from 0 (no depressive/anxious symptoms) to 42 (most severe symptoms)

a questionnaire rating non motor symptoms, ranging from 0 (no symptoms) to 128 (most severe non motor symptoms)

rates probability for the presence of RBD (REM sleep behavior disorder) using 13 questions; points are given from 0 to 13 with higher points indicating a higher probability for RBD

the GPAQ is a questionnaire provided by the WHO and rates the extent of physical (-in-) activity; rating is done according to the WHO manual available from the WHO website

a questionnaire rating quality of life specifically in ET patients; ranging from 0 (best quality of life) to 120 points (worst quality of life)

a smell test ranging from 0 (worst olfactory function) to 40 points (best olfactory function)

a screening cognitive test rating cognitive dysfunction from 0 (worst) to 30 (best)

assesses how well patients can remember 15 words after hearing them; the more they can remember, the better

patients need to translate specific symbols into numbers (1-9) using a key; they more the can translate in 90 seconds, the better

patients can look at 6 figures for 10 seconds each, then they have to reproduce them; 3 trials; the more they remember, the better

patients have to connect numbers (1 to 21) in ascending order with lines; time is measured in seconds; the faster, the better

patients have to connect numbers (1 to 13) and letters (A to L) in ascending order and alternatingly with lines; time is measured in seconds; the faster, the better

patients have to list words starting with "g" or "r" alternatingly or things within the categories of "clothes" or "flowers" alternatingly; they have 1 minute for each of the two tasks, the more they can list, the better

a quick questionnaire (5 questions) rating quality of life, ranging from 0 (very bad) to 1 (best)

a quick questionnaire rating resilience, ranging from 13 (least resilience) to 91 points (highest resilience)

a quick questionnaire rating sleep quality, ranging from 0 (best sleep) to 21 points (worst sleep quality)

patients are asked to draw Archimedes spirals (a total of 4, 2 with each hand) on a standard tablet PC using a touchpen; the process is done using a free available website-based application (http://www.trsper.com/); the main outcome is visual rating of the spirals ranging from 0 (perfectly normal) to 9 (worst spiral)

blood pressure test for orthostatic hypotension; blood pressure is measured non-invasively using a automatic device at the left arm in seating position and after 1 and 3 minutes of standing; orthostatic hypotension is defined as a drop in systolic blood pressure of 20mmHg or more and/or of diastolic blood pressure of 10mmHg or more

sGFAP-level is measured from serum using SIMOA-technology

sNfL-level is measured from serum using SIMOA-technology

the presence of hyperechogenicity (yes/no and area in cm2) of the substantia nigra is measured using transcranial sonography

tremor frequency and total tremor power are measured

white matter hyperintensities (volume in mm3)

presence of lacunes (number of)

cerebral microbleeds (number of)

volumetry of total brain and regions (in mm3)

Diffusion tensor imaging parameters (fractional anisotropy, mean diffusivity, radial diffusivity)

nigrosome-1-imaging (presence of swallow tail sign yes vs. no)

thickness of retinal nerve fiber layer in both eyes and each quadrant and in vicinity of the macula and papilla

thickness of ganglion cell layer in both eyes and each quadrant and in vicinity of the macula and papilla

thickness of inner plexiform layer in both eyes and each quadrant and in vicinity of the macula and papilla

thickness of choroidea in both eyes and each quadrant and in vicinity of the macula and papilla

swab of the olfactory mucosa testing for alpha-synuclein using a seeding assay (outcome: presence of misfolded alpha-synuclein yes vs. no)