Identification of mutations in the PARK2 gene in Serbian patients with Parkinson's disease.

Mutations in the PARK2 (PRKN) gene are the most common cause of autosomal-recessive (AR) juvenile parkinsonism and young-onset Parkinson's disease (YOPD). >100 different variants have been reported, including point mutations, small indels and single or multiple exon copy number variations. Mutation screening of PARK2 was performed in 225 Serbian PD patients (143 males and 82 females) with disease onset before 50 years and/or positive family history with apparent AR inheritance. All coding regions and their flanking intronic sequences were amplified and directly sequenced. Whole exon multiplications or deletions were detected using Multiple Ligation Probe Amplification (MLPA) method. We identified 12 PD patients with PARK2 mutations (5.3%). Five patients (2.2%) had biallelic mutations and seven (3.1%) were single mutation carriers. Patients with compound heterozygous mutations had earlier onset of the disease compared to non-carriers (p = 0.005) or heterozygotes (p = 0.001). Other clinical features in mutation carriers were not different compared to non-carriers. In our cohort, sequence and dosage variants were equally represented in patients, inducing their first symptoms mainly before the age of 30. For efficient genetic testing strategy, patients with early, especially juvenile onset of PD were strong candidates for both dosage and sequence variants screening of PARK2 gene.

Brain structural and functional signatures of impulsive-compulsive behaviours in Parkinson's disease.

This study assessed brain structural and functional alterations in patients with Parkinson's disease and impulsive-compulsive behaviours (PD-ICB) compared with controls and PD no-ICB cases. Eighty-five PD patients (35 PD-ICB) and 50 controls were recruited. All subjects underwent three-dimensional T1-weighted, diffusion tensor (DT), and resting state functional magnetic resonance imaging (RS fMRI). We assessed cortical thickness with surface-based morphometry, subcortical volumes using FIRST, DT MRI metrics using region of interest and tractography approaches, and RS fMRI using a model free approach. Compared with controls, both PD groups showed a pattern of brain structural alterations in the basal ganglia (more evident in PD no-ICB patients), sensorimotor and associative systems. Compared with PD no-ICB, PD-ICB cases showed left precentral and superior frontal cortical thinning, and motor and extramotor white matter tract damage. Compared with controls, all patients had an increased functional connectivity within the visual network. Additionally, PD no-ICB showed increased functional connectivity of bilateral precentral and postcentral gyri within the sensorimotor network compared with controls and PD-ICB. Severity and duration of PD-ICB modulated the functional connectivity between sensorimotor, visual and cognitive networks. Relative to PD no-ICB, PD-ICB patients were characterised by a more severe involvement of frontal, meso-limbic and motor circuits. These data suggest ICB in PD as the result of a disconnection between sensorimotor, associative and cognitive networks with increasing motor impairment, psychiatric symptoms, and ICB duration. These findings may have important implications in understanding the neural substrates underlying ICB in PD.

Transcranial sonography in dopa-responsive dystonia.

BACKGROUND AND PURPOSE: Mutations in the GCH1 gene, encoding GTP cyclohydrolase 1, the enzyme critically important for dopamine production in nigrostriatal neurons, are the most common cause of dopa-responsive dystonia (DRD), characterized predominantly by limb dystonia, although parkinsonian features may also be present. It has been suggested that DRD is a neurochemical rather than neurodegenerative disorder. METHODS: Transcranial brain sonography, which might be a risk marker for nigral injury, was obtained from 141 subjects divided into four groups: (i) 11 patients with genetically confirmed DRD; (ii) 55 consecutive patients with Parkinson's disease (PD); (iii) 30 patients diagnosed as isolated adult-onset focal dystonia; and (iv) 45 healthy controls (HCs). RESULTS: Substantia nigra hyperechogenicity was present in 63.6% of patients with DRD, which was significantly different in comparison to patients with dystonia (20%) and HCs (6.7%), but not in comparison to the PD group (87.3%). Also, values of the maximal areas of substantia nigra hyperechogenicity in patients with DRD were higher in comparison to HCs, but significantly lower than among the PD group. CONCLUSIONS: We suggested that the observed transcranial brain sonography features in patients with DRD might primarily be risk markers for particular clinical features (parkinsonism, dystonia) occurring in the specific genetic context (i.e. GCH1 mutations), or might reflect compensated neurodegenerative processes triggered by the long-lasting dopamine deficiency due to the profound delay in levodopa treatment in our patients with DRD.

Comparison of temporal and stride characteristics in myotonic dystrophies type 1 and 2 during dual-task walking.

OBJECTIVE: We analyzed temporal and stride characteristics in patients with myotonic dystrophy type 1 (DM1) and type 2 (DM2) while performing dual mental and motor tasks, and investigated correlations between gait parameters and cognitive impairments. METHOD: Dual-task walking was performed by 37 patients (20 DM1 and 17 DM2) and 48 healthy subjects divided into two groups, age- and gender-matched control group for DM1 (HC1) and age- and gender-matched control group for DM2 (HC2). The subjects performed a basic walking task, dual-motor task, dual-mental task, and combined motor and mental task. RESULTS: DM1 and DM2 patients differed significantly in temporal and stride characteristics compared to HC. Main differences in DM1 were slower gait and shorter stride length, while both DM1 and DM2 patients had a higher degree of variation of the swing time during dual-task gait, a parameter that reflects posture and balance. Impact of the cognitive dual task on gait pattern changes was also observed. Visuospatial ability correlated with gait changes in DM1, while executive functions had stronger influence in DM2 (p<0.01). Both patient groups had leg muscle weakness. CONCLUSION: Gait pattern was impaired in both patient groups concerning temporal and stride characteristics. Dual-task walking paradigm may discover mild initial gait changes and could provide early identification of fall risks and predict possible falls in DM patients.

Management of dystonia in Europe: a survey of the European network for the study of the dystonia syndromes.

BACKGROUND AND PURPOSE: Dystonia is difficult to recognize due to its large phenomenological complexity. Thus, the use of experts in dystonia is essential for better recognition and management of dystonia syndromes (DS). Our aim was to document managing strategies, facilities and expertise available in various European countries in order to identify which measures should be implemented to improve the management of DS. METHODS: A survey was conducted, funded by the Cooperation in Science and Technology, via the management committee of the European network for the study of DS, which is formed from representatives of the 24 countries involved. RESULTS: Lack of specific training in dystonia by general neurologists, general practitioners as well as other allied health professionals was universal in all countries surveyed. Genetic testing for rare dystonia mutations is not readily available in a significant number of countries and neurophysiological studies are difficult to perform due to a lack of experts in this field of movement disorders. Tetrabenazine is only readily available for treatment of dystonia in half of the surveyed countries. Deep brain stimulation is available in three-quarters of the countries, but other surgical procedures are only available in one-quarter of countries. CONCLUSIONS: Internationally, collaboration in training, advanced diagnosis, treatment and research of DS and, locally, in each country the creation of multidisciplinary teams for the management of dystonia patients could provide the basis for improving all aspects of dystonia management across Europe.

Cerebrospinal fluid biomarkers of neurodegeneration in patients with juvenile and classic myotonic dystrophy type 1.

BACKGROUND AND PURPOSE: The aim of the present study was to analyze cerebrospinal fluid (CSF) levels of total tau (T-tau), phosphorylated tau (P-tau) and the 42-amino-acid form of ß-amyloid (Aß42 ) in patients with myotonic dystrophy type 1 (DM1), and their possible correlations with cognitive and behavioral manifestations in these patients. METHODS: Lumbar puncture was performed in 74 patients with DM1 [27 with the childhood/juvenile form (jDM1) and 47 with the adult form (aDM1) of the disease] and 26 control subjects who were subjected to orthopedic surgery. Sandwich ELISA was used for measuring the levels of T-tau, P-tau and Aß42. RESULTS: The CSF level of Aß42 was at its lowest in patients with jDM1 and at its highest in controls (P < 0.05). A tendency of T-tau and P-tau to increase was greater in aDM1 patients than in jDM1 patients and controls (P > 0.05). In both jDM1 and aDM1 patients, significant correlations were found between Aß42 and T-tau (rho = 0.81 and rho = 0.67, respectively, P < 0.01), as well as between Aß42 and P-tau (rho = 0.87 and rho = 0.67, respectively, P < 0.01). The Aß42/P-tau ratio decreased with age in aDM1 patients (rho = -0.30, P < 0.05). Only the level of Aß42 in the CSF of jDM1 patients was correlated with the size of the CTG expansion (rho = -0.53, P < 0.05). Only a few correlations were observed between levels of biomarkers and neuropsychological testing. CONCLUSION: The CSF level of Aß42 was decreased in patients with jDM1, whilst the Aß42/P-tau ratio was decreased in aDM1 patients. Positive correlations between Aß42 , T-tau and P-tau were observed in both forms of disease. Further studies with larger cohorts of DM1 patients are necessary.

The significance of the ultrasound diagnostics in evaluation of the emboligenic pathogenesis of transient ischemic attacks.

The objective of this study was to examine the possibilities of ultrasound diagnostics in the evaluation of emboligenic pathogenesis of transient ischemic attacks (TIAs) and the frequency of specific origins of embolism. A total of 150 adult patients with TIA and 50 control patients, were examined by neurosonologic, echocardiographic and venous ultrasound examination. Emboligenic pathogenesis of TIA was established in 36.6% of patients. Microembolic signals were detected in 22.7% of the whole group, and 61.8% in emboligenic TIA subgroup. Artery-to-artery embolism from ulcerated plaque of the carotid arteries was found in 12.6% of patients, from the aortic arch atheroma in 3.3% and cardioembolism in 12.6% (atrial fibrillation 7.3%, atrial septal aneurysm 2%, mitral valve prolapse 2%, mechanical heart valve 0.7%, left atrium thrombus 0.7%). Paradoxic embolism with the patent foramen ovale was established in 6% of patients, and with the pulmonary right-to-left shunt in 2%. Correlation with controls showed significantly higher frequency of the ulcerated carotid plaque and frequency of microembolic signals in the TIA group (p < 0.05). The patients with potential sources of embolism had a greater risk of developing TIA than those without these sources.

Summary of the recommendations of the EFNS/MDS-ES review on therapeutic management of Parkinson's disease.

OBJECTIVE: To summarize the 2010 EFNS/MDS-ES evidence-based treatment recommendations for the management of Parkinson's disease (PD). This summary includes the treatment recommendations for early and late PD. METHODS: For the 2010 publication, a literature search was undertaken for articles published up to September 2009. For this summary, an additional literature search was undertaken up to December 2010. Classification of scientific evidence and the rating of recommendations were made according to the EFNS guidance. In cases where there was insufficient scientific evidence, a consensus statement ('good practice point') is made. RESULTS AND CONCLUSIONS: For each clinical indication, a list of therapeutic interventions is provided, including classification of evidence.

EFNS/MDS-ES/ENS [corrected] recommendations for the diagnosis of Parkinson's disease.

BACKGROUND: A Task Force was convened by the EFNS/MDS-ES Scientist Panel on Parkinson's disease (PD) and other movement disorders to systemically review relevant publications on the diagnosis of PD. METHODS: Following the EFNS instruction for the preparation of neurological diagnostic guidelines, recommendation levels have been generated for diagnostic criteria and investigations. RESULTS: For the clinical diagnosis, we recommend the use of the Queen Square Brain Bank criteria (Level B). Genetic testing for specific mutations is recommended on an individual basis (Level B), taking into account specific features (i.e. family history and age of onset). We recommend olfactory testing to differentiate PD from other parkinsonian disorders including recessive forms (Level A). Screening for pre-motor PD with olfactory testing requires additional tests due to limited specificity. Drug challenge tests are not recommended for the diagnosis in de novo parkinsonian patients. There is an insufficient evidence to support their role in the differential diagnosis between PD and other parkinsonian syndromes. We recommend an assessment of cognition and a screening for REM sleep behaviour disorder, psychotic manifestations and severe depression in the initial evaluation of suspected PD cases (Level A). Transcranial sonography is recommended for the differentiation of PD from atypical and secondary parkinsonian disorders (Level A), for the early diagnosis of PD and in the detection of subjects at risk for PD (Level A), although the technique is so far not universally used and requires some expertise. Because specificity of TCS for the development of PD is limited, TCS should be used in conjunction with other screening tests. Conventional magnetic resonance imaging and diffusion-weighted imaging at 1.5 T are recommended as neuroimaging tools that can support a diagnosis of multiple system atrophy (MSA) or progressive supranuclear palsy versus PD on the basis of regional atrophy and signal change as well as diffusivity patterns (Level A). DaTscan SPECT is registered in Europe and the United States for the differential diagnosis between degenerative parkinsonisms and essential tremor (Level A). More specifically, DaTscan is indicated in the presence of significant diagnostic uncertainty such as parkinsonism associated with neuroleptic exposure and atypical tremor manifestations such as isolated unilateral postural tremor. Studies of [(123) I]MIBG/SPECT cardiac uptake may be used to identify patients with PD versus controls and MSA patients (Level A). All other SPECT imaging studies do not fulfil registration standards and cannot be recommended for routine clinical use. At the moment, no conclusion can be drawn as to diagnostic efficacy of autonomic function tests, neurophysiological tests and positron emission tomography imaging in PD. CONCLUSIONS: The diagnosis of PD is still largely based on the correct identification of its clinical features. Selected investigations (genetic, olfactory, and neuroimaging studies) have an ancillary role in confirming the diagnosis, and some of them could be possibly used in the near future to identify subjects in a pre-symptomatic phase of the disease.

Glucocerebrosidase mutations in a Serbian Parkinson's disease population.

BACKGROUND AND PURPOSE: To screen for glucocerebrosidase (GBA) mutations in a Serbian Parkinson's disease (PD) population. METHODS: Glucocerebrosidase exons 8-11 harbouring the most common mutations were sequenced in 360 patients with PD and 348 controls from Serbia. Haplotype analysis was performed for the N370S mutation and compared with German and Ashkenazi Jewish carriers. RESULTS: Glucocerebrosidase mutations were significantly more frequent in patients with PD (21/360; 5.8%) vs. controls (5/348; 1.4%; OR = 4.25; CI, 1.58-11.40; P = 0.0041). Two patients with PD carried homozygous or compound heterozygous mutations in GBA. The N370S mutation accounted for about half of the mutated alleles in patients (10/23) but was absent amongst controls. Three novel variants were detected including two non-synonymous variants (D380V, N392S) in the patient group and one synonymous change (V459V) in a control. Carriers of the D409H mutation were also sequenced for H255Q, and all were found to carry the [D409H; H255Q] double-mutant allele. Genotyping suggested a common haplotype for all N370S carriers. CONCLUSION: Glucocerebrosidase mutations represent a PD risk factor in the Serbian population.

Transcranial brain sonography findings in two main variants of progressive supranuclear palsy.

BACKGROUND AND PURPOSE: Progressive supranuclear palsy (PSP) can occur with two main clinical presentations, classified as classical Richardson's syndrome (PSP-RS) and as PSP-parkinsonism (PSP-P), the most common atypical PSP variant. The differential diagnosis between them is challenging. Therefore, we studied different ultrasound markers by transcranial sonography in individuals with PSP-RS and PSP-P, to test their value in the diagnostic work up of these patients. METHODS: Transcranial sonography was performed in 21 patients with PSP-RS and 11 patients with PSP-P. Echogenic sizes of the substantia nigra (SN) and the lenticular nuclei (LN), as well as the width of the third ventricle, were measured. RESULTS: Among the patients with PSP-RS and PSP-P, three (14%) and eight (73%) patients had a hyperechogenic SN (P = 0.020), respectively. Uni- or bilateral hyperechogenicity of the LN was observed in 67% and 36% of patients with PSP-RS and PSP-P, respectively (P = 0.101). Third ventricle was significantly wider in patients with PSP-RS (11.2 ±â€…2.3 mm) when compared with patients with PSP-P (7.5 ±â€…1.4 mm; P = 0.001). CONCLUSION: Our data, possibly reflecting pathological differences, primarily contribute supporting the view that the neurodegenerative process differs in the two PSP variants.

History of exposure to dopaminergic medication does not affect motor cortex plasticity and excitability in Parkinson's disease.

OBJECTIVE: Little is known whether and how chronic exposure to dopaminergic treatment alters physiological mechanisms in Parkinson's disease (PD). METHODS: Two clinically similar groups of PD patients, one consisting of drug-naïve patients and another of patients already on chronic dopaminergic medication (when off medication), were compared to each other and to a control group. Plasticity and excitability of the hand primary motor cortex of the more affected side were evaluated using transcranial magnetic stimulation (TMS) techniques. RESULTS: There was little difference between two patient groups, and both groups showed similar differences in comparison to controls: decreased facilitatory sensory-motor plasticity (as measured by paired associative stimulation [PAS] protocol), impaired short-interval intracortical inhibition (SICI), and diminished slope of input-output curves at higher TMS intensities. The exception was that 30 min after PAS, intracortical facilitation (ICF) was significantly reduced in drug-naïve patients, whereas it changed much less in other two groups. CONCLUSIONS: Chronic exposure to dopaminergic drugs does not affect substantially the features of motor cortex excitability and plasticity in PD. There is little interaction between plasticity and excitability features of motor cortex in PD. SIGNIFICANCE: Reduced response to facilitatory PAS protocol, reduced SICI, and reduced slope of the input-output curve at higher TMS pulse intensities, seem to be physiological markers for the presence of the pathological disease process in PD. Long term treatment does not seem to change the underlying physiology of the disease.

A genome-wide survey and functional brain imaging study identify CTNNBL1 as a memory-related gene.

Unbiased genome-wide screens combined with imaging data on brain function may identify novel molecular pathways related to human cognition. Here we performed a dense genome-wide screen to identify episodic memory-related gene variants. A genomic locus encoding the brain-expressed beta-catenin-like protein 1 (CTNNBL1) was significantly (P=7 × 10(-8)) associated with verbal memory performance in a cognitively healthy cohort from Switzerland (n=1073) and was replicated in a second cohort from Serbia (n=524; P=0.003). Gene expression studies showed CTNNBL1 genotype-dependent differences in beta-catenin-like protein 1 mRNA levels in the human cortex. Functional magnetic resonance imaging in 322 subjects detected CTNNBL1 genotype-dependent differences in memory-related brain activations. Converging evidence from independent experiments and different methodological approaches suggests a role for CTNNBL1 in human memory.

Vascular risk factors in Alzheimer's disease - preliminary report.

BACKGROUND: The vascular risk factors are associated with an increased risk for vascular cognitive decline (VCD), but also with Alzheimer disease (AD). OBJECTIVE: To investigate vascular risk factors in relation to AD and VCD, with a non-invasive neurosonological methods in a clinical settings. RESULTS: A total of 296 patients with AD and 237 patients with VCD were included in the study. Hypertension, hyperlipidemia, diabetes mellitus, stroke, and white matter changes (p<0.001) were significantly more prevalent in VCD, although they were also present in AD patients. No statistically significant differences were obtained between groups regarding coronary disease, atrial fibrillation, average degree of carotid artery stenosis and carotid intima-media thickness (cITM). However, the patients with AD had carotid artery stenosis ">50%" (p=0.007) and present plaques (p<0.001) more frequently compared to vascular group. The significant associations between robust cognitive measure and vascular factors, diabetes mellitus, carotid stenosis, cITM, and type of plaques were identified only in VCD, but not in AD group. CONCLUSIONS: The vascular risk factors were more prevalent in VCD group, although they were also present in AD. With few treatment options available in AD, it may be important not to neglect the vascular risk factors.

Are irreversible morphological [corrected] signs of portal hypertension in neurological form of Wilson's disease associated with treatment delay? A pilot study.

Aim of this study was to evaluate the rate of morphological liver and spleen abnormalities in patients with neurological clinical presentation of Wilson's disease (WD). Fourteen patients with neurological presentation of WD divided into group A (5 patients who initiated chelating therapy <24 months from the first symptoms) and group B (9 patients whose therapy started ≥24 months after the initial symptoms) underwent abdominal MRI examination. Abnormal findings on abdominal MRI were present in 28% of patients with neurological form of WD. Significant hepatosplenomegaly was present in none of the patients from group A and in 4 (44%) patients from group B. In addition, macronodular liver cirrhosis and peritoneal effusion were evident in two and one patient from group B, respectively, and in none of the patients from group A. Our results suggest that severe portal hypertension and liver damage in patients with neurological presentation of WD might be reversible or do not even develop if chelating treatment is initiated <2 years after the onset of symptoms.

Pattern of brain tissue loss associated with freezing of gait in Parkinson disease.

OBJECTIVE: To investigate whether a specific pattern of gray matter (GM) tissue loss is associated with freezing of gait (FOG) in patients with Parkinson disease (PD). METHODS: Seventeen patients with PD with FOG (PD-FOG), 20 patients with PD with no FOG (PD-noFOG), and 34 healthy control subjects were recruited. PD-FOG and PD-noFOG patients were matched on an individual basis for age, disease duration, and Hoehn and Yahr stage. Patients were also administered a comprehensive neuropsychological battery focused on executive functions. The extent and distribution of GM atrophy were assessed using voxel-based morphometry. RESULTS: In patients with PD, the severity of FOG correlated with frontal executive deficits. Compared with healthy control subjects, PD-FOG patients showed a distributed pattern of GM atrophy including the dorsolateral prefrontal, medial, and lateral temporal, inferior parietal, and occipital cortices. PD-noFOG patients showed only small regions of GM atrophy in the bilateral frontal and temporal cortex. The left inferior frontal gyrus, left precentral gyrus, and left inferior parietal gyrus were more atrophic in PD-FOG patients relative to both healthy control subjects and PD-noFOG patients. In PD-FOG patients, the severity of FOG was associated with GM volumes of the frontal and parietal cortices bilaterally. CONCLUSIONS: GM frontal and parietal atrophy occur in PD-FOG patients. FOG in PD seems to share with executive dysfunction and perception deficits a common pattern of structural damage to the frontal and parietal cortices.

Apathy and depression in Parkinson's disease: the Belgrade PD study report.

Apathy and depression are among the most common psychiatric and behavioral disorders associated with Parkinson's disease (PD). The objective of this study was to examine the prevalence and demographic and clinical correlates of apathy and depression in a clinical population-based sample of patients with PD and to assess whether apathy may present as a primary behavioral disturbance independent from depression and cognitive impairment. A series of 360 PD patients underwent psychiatric investigation with the Starkstein's Apathy Scale (AS), and the 17-item Hamilton Depression Rating Scale (HDRS-17), motor scoring with Hoehn and Yahr (HY) staging, and the Unified Parkinson's Disease Rating Scale (UPDRS); and cognitive screening with the Mini-Mental State Examination (MMSE) on the same day. Apathy coexisted with depression in 133 (36.9%) of PD patients, compared with depression without apathy in 16 (4.4%), apathy without depression in 84 (23%), and neither apathy nor depression in 127 PD patients (35.2%). Apathy was associated with higher axial UPDRS impairment score, lower MMSE score, higher l-dopa dosage, and earlier HY stages, while depression was predicted by the more advanced HY stages and younger age of PD patients. These findings suggest that apathy and depression may be separable in PD, although both are common in patients with PD. Therefore these two conditions should be systematically screened and considered in the care and management of PD.

Overcoming the clinical-MR imaging paradox of multiple sclerosis: MR imaging data assessed with a random forest approach.

BACKGROUND AND PURPOSE: In MS, the relation between clinical and MR imaging measures is still suboptimal. We assessed the correlation of disability and specific impairment of the clinical functional system with overall and regional CNS damage in a large cohort of patients with MS with different clinical phenotypes by using a random forest approach. MATERIALS AND METHODS: Brain conventional MR imaging and DTI were performed in 172 patients with MS and 46 controls. Cervical cord MR imaging was performed in a subgroup of subjects. To evaluate whether MR imaging measures were able to correctly classify impairment in specific clinical domains, we performed a random forest analysis. RESULTS: Between-group differences were found for most of the MR imaging variables, which correlated significantly with clinical measures (r ranging from -0.57 to 0.55). The random forest analysis showed a high performance in identifying impaired versus unimpaired patients, with a global error between 7% (pyramidal functional system) and 31% (Ambulation Index) in the different outcomes considered. When considering the performance in the unimpaired and impaired groups, the random forest analysis showed a high performance in identifying patients with impaired sensory, cerebellar, and brain stem functions (error below 10%), while it performed poorly in defining impairment of visual and mental systems (error of 91% and 70%, respectively). In analyses with a good level of classification, for most functional systems, damage of the WM fiber bundles subserving their function, measured by using DTI tractography, had the highest classification power. CONCLUSIONS: Random forest analysis, especially if applied to DTI tractography data, is a valuable approach, which might contribute to overcoming the MS clinical-MR imaging paradox.

Scaling analysis of bilateral hand tremor movements in essential tremor patients.

Recent evidence suggests that the dynamic-scaling behavior of the time-series of signals extracted from separate peaks of tremor spectra may reveal existence of multiple independent sources of tremor. Here, we have studied dynamic characteristics of the time-series of hand tremor movements in essential tremor (ET) patients using the detrended fluctuation analysis method. Hand accelerometry was recorded with (500 g) and without weight loading under postural conditions in 25 ET patients and 20 normal subjects. The time-series comprising peak-to-peak (PtP) intervals were extracted from regions around the first three main frequency components of power spectra (PwS) of the recorded tremors. The data were compared between the load and no-load condition on dominant (related to tremor severity) and non-dominant tremor side and with the normal (physiological) oscillations in healthy subjects. Our analysis shows that, in ET, the dynamic characteristics of the main frequency component of recorded tremors exhibit scaling behavior. Furthermore, they show that the two main components of ET tremor frequency spectra, otherwise indistinguishable without load, become significantly different after inertial loading and that they differ between the tremor sides (related to tremor severity). These results show that scaling, a time-domain analysis, helps revealing tremor features previously not revealed by frequency-domain analysis and suggest that distinct oscillatory central circuits may generate the tremor in ET patients.