Primary orthostatic tremor (ORPHA:238606)
A rare tremor disorder characterized by an isolated high frequency (>12 Hz) tremor that occurs when standing, typically in weight-bearing muscles, causing a feeling of unsteadiness or discomfort, which disappears when not standing.
Epidemiology
Prevalence is unknown, however, hundreds of cases have been reported all over the world, with female preponderance (sex ratio: 2:1), and a mean onset around 55-60 years old (range 13-85).
Clinical description
Primary orthostatic tremor (POT) appears on standing and is associated with an intense and disabling sense of unsteadiness, a fear of falling, discomfort, dizziness, shaking, trembling sensations and/or trembling of limbs and trunk. An action tremor (5-10 Hz) may be present in the arms. Symptoms during stance are reduced/abolished by walking, support, sitting, and lying down. Patients often shuffle, wobble, or seek support when standing. Prevalent signs during stance and walking are bent knees, hem sign (trembling of hem of skirt/shirt), and a broad base of support. Tandem gait may be abnormal (with normal heel-to-shin test). The fast tremor may be visible, palpable, and muscle auscultation may reveal a thudding sound (helicopter sign). The 'Orthostatic Tremor Severity and Disability Scale (OT-10)' is an online-available self-report scale which captures OT-related severity and disability based on the presentation of symptoms, such as unsteadiness, discomfort, or shaking when standing, and how they affected the patient's activities of daily living over the course of their past week. The term orthostatic tremor plus is used when OT is accompanied by other neurological symptoms.
Etiology
The pathophysiology of POT is unknown. Strong intermuscular coherence at tremor frequency, also between bilateral head muscles, is thought to be driven by a supraspinal (possibly cerebellar or brainstem) oscillator. The oscillator may also be active in healthy subjects who are made unsteady; POT may represent an exaggerated activity in otherwise physiological pathways involved in postural responses. An alternative hypothesis is that POT is triggered by the weight of the body when standing still, and that the slight imbalance which ensues aggravates the tremor.
Diagnostic methods
Diagnosis is based on clinical examination of symptoms. The diagnostic procedure consists in confirmation of >12 Hz tremor in weight-bearing muscles during stance and absence after sitting (by electromyography) and not placing weight on the feet. There should be no extrapyramidal, cerebellar and/or other signs (except arm tremor), nor abnormal findings at adaptive optics (AO) imaging, electroneurography, or blood tests, which might point to OT-plus, secondary OT, or a comorbidity.
Differential diagnosis
Differential diagnoses include AO slow OT (4-12 Hz), orthostatic myoclonus (irregular bursts), essential tremor, Parkinson's disease, functional neurological disorder, restless legs syndrome, polyneuropathy, neurogenic claudication, and vertigo.
Genetic counseling
A positive family history is rare.
Management and treatment
There is no cure or standard treatment for POT. Effective medication includes benzodiazepines (clonazepam), anti-seizure medication (gabapentin and perampanel), and possibly beta-blockers (propranolol). Treatment response can be poor or wear off, and side-effects can limit daily dosages. Surgical treatment, described in limited numbers of medication refractory patients, includes deep brain stimulation, which showed (variable) improved ability to stand still, possibly diminishing over time, and side-effects. Bilateral spinal cord stimulation improved ability to stand for a majority of patient but had no effect in some. Physical aids (portable/high stool), training muscle strength, conditioning, medical statement and patient brochure/leaflet might be helpful.
Prognosis
POT is often slowly progressive. Severity of symptoms, effect of treatment, and experienced quality of life vary largely between patients.

                            Last update: 
                            February 2024


                            - Expert reviewer(s): 
                            Dr Anne-Fleur VAN ROOTSELAAR