Primary orthostatic tremor (POT) is a rare progressive neurological disorder with a high-frequency tremor while standing. The pathophysiology remains uncertain, and imaging studies have been inconclusive. The primary objective was to assess whether neurodegenerative changes are detectable in POT by quantitative susceptibility mapping (QSM) on brain MRI. A second objective was to explore volumetric changes in subcortical grey matter and cerebellum. In this cross-sectional study, 20 participants with POT and 14 age- and sex-matched healthy controls (HCs) were examined using a 3 T Siemens Prisma scanner with a T2*-weighted multiecho gradient-echo sequence for QSM. Regions of interest (ROIs) were automatically and manually segmented. Selected ROIs were the red nucleus, globus pallidus (GP), thalamus, caudatus, putamen, substantia nigra, dentate nucleus and inferior and superior colliculus. There was a significant increase in susceptibility in the red nucleus (mean susceptibility 138.1 parts per billion (ppb) in POT and 113.3 ppb in HC, p=0.015) and GP (mean susceptibility 101.2 ppb in POT and 73.3 ppb in HC, p=0.0015) and a significantly lower volume of the GP in the POT group compared with HC (mean volume 3838 mm3 in POT and 4062 mm3 in HC, p=0.012). Increased susceptibility and decrease of volume indicate the possibility of a neurodegenerative process affecting the red nucleus and GP in POT. The red nucleus and GP are involved in motor control, and a focal dysfunction in these networks may be a part of the cause of orthostatic tremor.

Orthostatic tremor (OT) is a rare, heterogenous disorder, recently sub-classified into primary OT (isolated 13-18 Hz tremor), OT-plus (OT with additional neurological features) and pseudo-OT (OT with frequencies < 13 Hz). However, to our knowledge no study to date has compared clinical characteristics between all three subgroups. We aim to further define and compare the clinical characteristics of the three different OT subgroups, utilising one of the largest described single centre cohorts to date. A retrospective analysis was undertaken of clinical records from 74 OT patients at Charing Cross Hospital between 1999 and 2023, enabling categorisation into subgroups. Clinical characteristics, including treatment efficacy and overall disability, were subsequently described and compared between subgroups. 61 primary OT, 5 OT-plus and 8 pseudo-OT patients were identified. Baseline demographics were comparable between subgroups. Logistic regression suggested age of onset (OR = 1.02, p = 0.229), symptom duration (OR = 1.05, p = 0.083), tremor frequency (OR = 1.02, p = 0.826) and subgroup (OT-plus (OR = 1.86, p = 0.565) and pseudo-OT (OR = 1.41, p = 0.683)) were not significant predictors of disability. Treatment response varied between subgroup, with primary OT and pseudo-OT patients more frequently reporting symptomatic improvement with clonazepam, gabapentin and/or alprazolam than OT-plus patients. We provide further insight into the clinical phenotypes of the OT subgroups and encourage future studies to validate these findings with larger sample sizes and establish reliable tools to measure OT severity to better assess disease progression and treatment response.

Orthostatic tremor (OT) and orthostatic myoclonus (OM) are rare weight-bearing hyperkinetic disorders defined electrophysiologically but often overlap clinically. Prior studies were limited to small series with little assessment of comorbidities, functional outcomes, or treatments. The Longitudinal Orthostatic Tremor Study (LOTS) was initiated to address these gaps through multidimensional phenotyping. Baseline data from 58 consecutively identified patients with OT or OM at a tertiary neurology center in India were analyzed. Clinical evaluation, surface electromyography (sEMG), neuroimaging, and comorbidity screening were performed. Severity was assessed with the OT-10 scale, functional status with the Orthostatic Tremor Impact Profile (OTIP), and quality of life with the 36-item Short Form Health Survey (SF-36). Variables were organized into five analytical domains-demographics, phenomenology, comorbidities, functional outcomes, and treatments-and compared across OT vs OM, primary vs secondary OT, and high- vs low-frequency OT. Fifty-two patients had OT (89.7%) and six had OM (10.3%). Demographics were broadly similar, though age was associated with high-frequency OT (P = .012). Phenomenological features overlapped, with twitching linked to secondary OT (P = .022). Dementia, polyneuropathy, and diabetes were more common in OM and secondary OT (P < .05). Functional outcomes were comparable, except for higher pain scores in secondary OT (P = .026). Clonazepam was most prescribed; other agents showed inconsistent associations. Baseline LOTS findings show broad overlap across diagnostic domains, indicating that sEMG-based labels alone do not capture heterogeneity. Multidimensional approaches, including Disease burden index and latent class analysis, may refine classification and guide individualized management. This study presents the first structured multidimensional phenotyping of orthostatic tremor and orthostatic myoclonus, integrating clinical, electrophysiological, comorbidity, functional, and treatment domains. Findings demonstrate diagnostic overlap and support multidimensional approaches for refining classification and guiding individualized management across orthostatic hyperkinetic syndromes.

Primary orthostatic tremor (POT) is a rare neurological disease presenting as a bilaterally coherent tremor of 13-18 Hz and a subjective sensation of unsteadiness while standing. Patients are severely affected by the inability to stand and often eventually referred to walking aids and dependence on others. This study aimed to investigate the clinical characteristics of POT in a Swedish patient population by interviews and questionnaires. Patients with POT were recruited nationwide in Sweden. All participants underwent neurological examination, structured interview and evaluation according to nine standardized rating scales and questionnaires, including the novel orthostatic tremor scales OTIP and OT-10. Fifty-two participants with EMG-verified POT were included in the final analysis. Disease duration was not significantly correlated to disease severity, while OTIP and OT-10 were highly correlated with severity of POT. Postural or action tremor in the arms were present in 58%. Mild signs of parkinsonism were common, and the combination of mild rigidity and bradykinesia was present in 25%. Symptoms of depression and anxiety were present in 25%. Although quality of life was often severely affected, 65% performed activities of daily life independently. Patients with POT may be severely affected by their disease, independently of disease duration. Multiple associated symptoms like tremor in the upper extremities and mild Parkinsonian features need to be recognized by healthcare professionals. 52 patients with POT were clinically examined with rating scales and questionnaires. Additional symptoms like other tremors, parkinsonian signs, and depressive symptoms were common. Disease severity did not correlate to additional symptoms or disease duration. Questionnaires like OTIP and OT-10 can be recommended for assessment of disease severity.

Primary orthostatic tremor (POT) is a rare movement disorder characterized by a high-frequency tremor and a considerable feeling of unsteadiness. People with POT are significantly affected in their daily activities and have reduced quality of life. The tremor occurs in standing position and dominates in the lower extremities. However, whether an orthostatic position is essential for evoking the tremor has not been fully clarified. To investigate how POT is responding to muscle load in non-orthostatic positions. In this work, we measured the tremor in POT patients using a smartphone running a tremor analysis application attached to the proximal fibula in supine, seated and standing position, as well as when they were subjected to muscle load in a leg press machine in a seated position. We demonstrate that the tremor can be elicited by muscle load while the patient is sitting, compatible with a weight-bearing isometric tremor, without the need to be in standing position. Furthermore, the weight of the load modulates the amplitude of the elicited tremor, but not its frequency. These findings suggest that POT is a weight-bearing hyperkinetic disorder and challenge the conventional assumption that the POT patient must be in standing position for the tremor to fully manifest. The results potentially have implications for understanding the mechanisms underlying POT, and can be of importance in future experimental studies, for example MRI, when standing position is not an available option.