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Objective Primary orthostatic tremor (OT) is a rare neurological disease of unknown pathophysiology characterized by a high-frequency tremor mainly of the legs when standing. The aim of this study was to examine its long-term course by subjective estimation and objective recording by serial posturography and to obtain further standardized epidemiological and clinical data on patients with OT. Methods A clinical cohort of 37patients with the diagnosis of primary OT was screened for this longitudinal follow-up study. Eighteen patients consented to participate. During study visit all patients underwent a standardized neurological examination and completed subjective scales and scores. Posturographic recordings at follow-up were compared to prior clinical posturographic measurements in 15cases. Results In our cohort the mean duration of symptoms was 14.1 ± 6.8 years. Subjectively, 78% of patients reported progression of the disease. Posturographic data (5.4 ± 4.0 years) revealed a significant increase of the total sway path (standing on firm ground with eyes open) from 2.4 ± 1.3 to 3.4 ± 1.4 m/min (p = 0.022) and of the total root mean square values from 9.8 ± 4.3 to 12.4 ± 4.8 mm (p = 0.028). None of these observations are explained by aging of the patients. Mean frequency of the tremor did not change over time (14.7 ± 1.9 Hz vs. 14.9 ± 2.0 Hz at follow-up). Clinically, most patients had signs of cerebellar dysfunction and a substantial portion also showed proprioceptive deficits in the long-term course. Conclusions This long-term follow-up study indicates, that primary OT is a progressive disorder. Furthermore, the clinical observation of cerebellar dysfunction in most OT patients in the long-term course might indicate an important role of the cerebellum in its pathophysiology. [ABSTRACT FROM AUTHOR]

Background and aim Primary orthostatic tremor (OT) is a rare neurological disease of unknown pathophysiology characterized by a high frequency tremor mainly of the legs when standing. The aim of the present study was to depict the cerebral tremor network in OT by [ 18 F]-FDG-PET during standing. Methods Ten patients (mean age 58 ± 12 years) with neurophysiologically proven OT (EMG, posturography) and ten age-matched healthy controls were included in the study. All subjects underwent a [ 18 F]-FDG-PET paradigm during real standing (i.e. injection of [ 18 F]-FDG during upright stance, PET scan 30 min p.i.). As a control condition in a second session a PET was acquired after injection of [ 18 F]-FDG in lying position. PET images were processed by SPM8 software and compared between groups and conditions. Results All patients but no control subject showed a characteristic high-frequency peak at 12–16 Hz in posturography. In healthy subjects the regional cerebral glucose metabolism (rCGM) during standing compared to lying was increased in the vermal cerebellum, thalamus and primary motor region. During standing, OT patients had a relatively increased rCGM in the cerebellum (including the dentate nucleus), the ventrointermediate nucleus of the thalamus and the primary and supplementary motor cortex bilaterally in comparison to the control group. A relatively decreased rCGM was found in the mesiofrontal cortical areas in OT patients during standing. Conclusions In the present study a cerebello–thalamo–cortical tremor network is depicted in a group of OT patients using [ 18 F]-FDG-PET during standing. The data strongly reinforce the idea that the ventrointermediate nucleus of the thalamus may be a therapeutic target for deep brain stimulation in OT. [ABSTRACT FROM AUTHOR]

Introduction A recent case series study showed significant improvements of symptoms in patients with cerebellar ataxia on medication with the amino acid acetyl- dl -leucine (Tanganil) ( Strupp et al., 2013 ). In analogy to electrophysiological studies in animals it was hypothesized that acetyl-DL-leucine modulates the activity of central vestibular neurons, preferably in the cerebellum, by normalizing the membrane potential of depolarized or hyperpolarized neurons and thereby improves central compensation. However, the mode of action of acetyl- dl -leucine and the site of central compensation remained speculative. To deepen our insights in the central compensatory processes induced by acetyl- dl -leucine we performed a FDG-PET study in cerebellar ataxic patients off and on treatment. Methods 21 patients with cerebellar ataxia of different etiologies were scanned by resting state FDG-PET twice, (A) off treatment (PET 1), and a second time (B) ⩾3 months on treatment with 5g/day acetyl- dl -leucine (PET 2; n = 18). At both time points the patients underwent a detailed neurological examination and measurements of standardized ataxia scales (SARA, SCAFI). Group subtraction analyses (PET 1 vs. PET 2; responders vs. non-responders) as well as statistical group comparisons with age- and gender-matched healthy controls were calculated with statistical parametric mapping (SPM). Results The contrast on vs. off treatment (PET 2 vs. PET 1) mainly showed signal differences in the mesencephalon (midbrain integration centers) as well as in the lateral medullary brainstem (vestibular nucleus region), thalami and midinsular regions bilaterally. The contrast PET 1 vs. PET 2 revealed signal differences in the posterior insula as well as in primary and secondary visual areas (including MT/V5) bilaterally. Restricting the analyses to treatment-responders ( n = 11), PET 2 vs. PET 1 showed similar signal areas in the central midbrain and dorsal medullary brainstem bilaterally that were lacking in the corresponding contrast of the non-responders ( n = 6). In the direct comparison of responders vs. non-responders PET 2 signal differences were located in both caudate nuclei, the superior temporal gyrus and hippocampus. The signal in responders – mainly in the posterior insula and the medial temporal gyrus – was lower compared to non-responders. In all contrasts cerebellar signal changes were sparse. Conclusions Central compensatory processes induced by acetyl- dl -leucine in cerebellar ataxia seem to involve mainly centers in the medulla (vestibular nuclei), midbrain (vestibular integration centers), thalami, basal ganglia and insular regions rather than neurons in the cerebellum, the primary site of dysfunction in cerebellar ataxia syndromes. [ABSTRACT FROM AUTHOR]