Slow Orthostatic Tremor: Review of the Current Evidence

Abstract

Background: Orthostatic tremor (OT) is defined as tremor in the legs and trunk evoked during standing. While the classical description is tremor of ≥13 Hz, slower frequencies are recognized. There is disagreement as to whether the latter represents a slow variant of classical OT, or different tremor disorder(s) given frequent coexistent neurological disease. Methods: A systematic literature search of PubMed was performed in February 2019 for "slow orthostatic tremor" and related terms which generated 573 abstracts, of which 61 were included. Results: Between 1970 and 2019, there were 70 cases of electrophysiologically confirmed slow OT. Two-thirds were female, of mean age 60 years (range 26-86), and mean disease duration 6 years (range 0-32). One-third of cases were isolated, and two-thirds had a coexistent disorder(s), including parkinsonism (30%), ataxia (12%), and dystonia (10%). Postural arm tremor was present in 34%. Median tremor frequency was 6-7 Hz (range 3-12). Tremor bursts ranged from 50 to 150 ms duration, and were alternating or synchronous in antagonistic and/or analogous muscles. Low and high coherences were reported. Five cases (7%) had coexistent classical OT. Clonazepam was the most effective medication across all frequencies, and levodopa was effective for 4-7 Hz OT with coexistent parkinsonism. Two cases resolved with the treatment of Graves' disease. Electrophysiology and imaging predominantly support a central tremor generator. Discussion: While multiple lines of evidence separate slow OT from classical OT, clinical and electrophysiological overlap may occur. Primary and secondary causes are identified, similar to classical OT. Further exploration to clarify these slow OT subtypes, clinically and neurophysiologically, is proposed.

What Shall We Do for the Patients with Shaky Leg Syndrome? A Review of 23 Patients

“…Generally, a regular high frequency (13-18 Hz) was the main characteristic of OT, such as primary OT, but low-frequency OT (< 13 Hz) was defined as slow OT (pseudo-OT) [3,4]. Slow OT is mostly associated with neurological diseases, such as ET, dystonia, and parkinsonism [19], and systemic diseases (e.g., multiple sclerosis, paraneoplastic syndrome, thiamine deficiency, Graves' disease) [14][15][16]20]. In addition, delayed-onset slow OT after head trauma and slow OT caused by structural lesions of the brain, such as pontine structures and left dorsolateral midbrain, were also reported [11][12][13].…”

“…Additionally, OT symptoms remained relatively unchanged, but in 6 of 41 cases (15%), the condition gradually progressed over time [17]. Hassan et al [19] reported that multiple medication trials were performed in 98 of 184 OT cases (53.3%). Among the medications tested, clonazepam was most effective, and betablockers, anticonvulsants, and carbidopa-levodopa had a mild benefit in regard to symptoms.…”

“…Among the medications tested, clonazepam was most effective, and betablockers, anticonvulsants, and carbidopa-levodopa had a mild benefit in regard to symptoms. However, the moderate effect of clonazepam diminished over time, leading to eventually using another drug [19]. The response to deep brain stimulation was not measured in the small number of cases.…”

Slow Orthostatic Tremor and the Case for Routine Electrophysiological Evaluation of All Tremors

“…In this issue of the journal, Hassan and Caviness reviewed the controversial topic of slow orthostatic tremor (OT). 1 Based on their review of the relevant literature, Hassan and Caviness concluded that “multiple lines of evidence separate slow OT from classical OT,” but they also noted that “clinical and electrophysiologic overlap may occur.” We were invited to discuss the significance of this overlap within the context of tremor classification.…”

“…The fairly routine performance of electrophysiological tests in patients with orthostatic shakiness has led to the discovery of slow OT and orthostatic myoclonus, which also have been reviewed by Hassan and Caviness. 1,17,18 Tremor frequency and coherence are only two of many measures that could prove useful in the characterization of other tremor syndromes. For example, tremor rhythmicity and frequency stability may be useful in distinguishing Parkinson tremor from essential tremor, 19 and many other electrophysiologic properties of tremor are being explored for their utility in tremor classification.…”