In vivo neurometabolic profiling in orthostatic tremor

Abstract

The pathogenesis of orthostatic tremor (OT) remains unclear, although some evidence points to dysfunction in the brainstem or cerebellum. We used single voxel proton magnetic resonance spectroscopy (1H-MRS) (3 T) to investigate whether neurochemical changes underlie abnormal cerebellar or cortical function in OT. Fourteen OT patients and 14 healthy controls underwent 1H-MRS studies with voxels placed in midparietal gray matter and cerebellum (vermis and central white matter). Spectral analysis was analyzed using the software package LCModel (version 6.3). The absolute metabolite concentrations and ratios of total N-acetylaspartate + N-acetylaspartyl glutamate (NAA), choline-containing compounds, myoinositol, and glutamate + glutamine to creatine were calculated. In midparietal gray matter spectra, we found a significant decrease in the absolute concentration of NAA in OT patients versus healthy controls (7.76 ± 0.25 vs 8.11 ± 0.45, P = 0.017). A similar decrease in NAA was seen in the cerebellar vermis (7.33 ± 0.61 vs 8.55 ± 1.54, P = 0.014) and cerebellar white matter (8.54 ± 0.79 vs 9.95 ± 1.57, P = 0.010). No differences in the other metabolites or their ratios were observed. Reductions in both cerebral cortical and cerebellar NAA suggest that there is neuronal damage or loss in OT, raising the intriguing question as to whether OT is a neurodegenerative disease. Along with clinical history and electrophysio0logical examination, 1H-MRS could serve as a useful diagnostic aid for OT.

Orthostatic Tremor: An Update on a Rare Entity

“… 92 A similar decrease in NAA was seen in the cerebellar vermis (7.33±0.61 vs. 8.55±1.54, p = 0.014) and cerebellar white matter (8.54±0.79 vs. 9.95±1.57, p = 0.010) of the cerebellum ( Figure 4 ). 92 No differences in the other metabolites or their ratios were observed. 92 Fourth, as in other neurodegenerative diseases 93 , 94 cognitive deficits, mainly in frontal executive function and memory, have been reported to occur in OT patients.…”

“… 5 , 9 , 43 Third, a reduction in cerebral cortical and cerebellar cortical viability in OT has been recently published. 92 Using proton magnetic resonance spectroscopy in a sample of 14 OT patients vs. 14 matched healthy controls, in mid-parietal gray matter spectra, a significant decrease in the absolute concentration of N -acetylaspartate+ N -acetylaspartyl (NAA) glutamate in the patients vs. the controls (7.76±0.25 vs. 8.11±0.45, p = 0.017) was observed. 92 A similar decrease in NAA was seen in the cerebellar vermis (7.33±0.61 vs. 8.55±1.54, p = 0.014) and cerebellar white matter (8.54±0.79 vs. 9.95±1.57, p = 0.010) of the cerebellum ( Figure 4 ).…”

Diffusion tensor imaging in orthostatic tremor: a tract‐based spatial statistics study

“…Clinical details of the OT patients have been published elsewhere . All 14 OT patients were right‐handed.…”

“…Participants were asked to bring all medications taken in the past 1 week to the clinic where the study researchers viewed and recorded the name and the dose of each one, with special emphasis on medications that potentially affect cognitive function (e.g., anxiolytics, stimulants, antipsychotics, antidepressants, antihistamines, or antiepileptics drugs). All participants underwent a neuropsychological assessment of cognitive functioning, including attention, executive function, visuospatial ability, verbal memory, visual memory, and language (Table ) . Depressive symptoms severity was assessed using the original 17‐item version of the Hamilton Depression Rating Scale …”

“…The pathogenesis of OT is unknown, although clinical and neuroimaging studies point to a role of the brainstem and cerebellum . As in other tremor disorders, such as essential tremor, the pathogenesis of OT may be related to changes in the cerebello‐thalamo‐cortical network (the so called “tremor” network) .…”