Heart rate variability in patients with essential tremor: A cross sectional study

To explore the incidence of depression in movement disorders and associated factors. A total of 121 Parkinson's disease (PD) patients from August 2010 to June 2011 and 62 ET patients from July 2009 to June 2010 were recruited. All of them were outpatients of our hospital. PD patients received the unified Parkinson's disease rating scale (UPDRS) -motor examination and a modified Hoehn and Yahr scale to stage the severity of their disorders while 62 essential tremor (ET) patients were evaluated with tremor rating scale for tremor-motor examination (items 1 - 15 of rating scale). All participants completed Hamilton depression rating scale (24 items) to measure the presence and degree of symptoms of depression. It was found that 56.2% of PD patients and 53.2% of ET patients were depressed (HAMD score of 8 or higher). Among them, the rates of mild depression were 38.9% and 35.5%, moderate depression 15.7% and 17.7% and severe depression 1.7% and 0% in PD and ET patients respectively. No significant differences existed between each group. The factor scores of cognitive impairment were 1.81 ± 1.86 and 1.04 ± 1.07 in PD and ET patients while those of sense of despair were 2.95 ± 1.97 and 4.09 ± 2.08 in each group. The differences had statistical significance in two factor scores of two groups (P < 0.05). No differences in anxiety/somatization, lose weight, day-and-night changes, block and sleep disorders between two groups. For PD patients, the motor score of UPDRS-III was positively correlated with total HAMD score (r = 0.511, P < 0.01). Similarly, for ET patients, tremor rating scale for tremor-motor subscale score and HAMD score were positively correlated (r = 0.828, P < 0.01). As two common movement disorders, PD and ET have a high incidence of depression. The severity of depression is similar in two groups. There is no significant intra-group difference in severity and frequency of depression. The most common symptoms are anxiety somatization, anhedonia, working difficulty, slowness and sleep disturbance. The depression and motor symptoms are positively correlated. Like the non-motor symptoms in PD, we should also pay attention to the non-motor symptoms in ET.

Early Experience With New Generation Deep Brain Stimulation Leads in Parkinson’s Disease and Essential Tremor Patients

Reliable electrophysiological indicators are urgently needed in the precise evaluation of Parkinson's disease (PD). It is still elusive whether oculomotor performance is impaired or has clinical value in early PD. This study aims to explore oculomotor performance in newly diagnosed, drug-naïve PD and its correlation with clinical phenotype. Seventy-five patients with de novo PD, 75 patients with essential tremor (ET), and 46 gender-and age-matched healthy controls (HCs) were included in this cross-sectional study. All subjects underwent oculomotor test via videonystagmography. Visually guided saccade latency, saccadic accuracy and gain in smooth pursuit eye movement (SPEM) at three frequencies of the horizontal axis were compared among the three groups. Patients with PD also received detailed motor and non-motor evaluation by serial scales. The association between key oculomotor parameters and clinical phenotypes were explored in PD patients. Both de novo PD and ET patients showed prolonged saccadic latency and decreased saccadic accuracy relative to HCs. SPEM gain in PD was uniformly reduced at each frequency. SPEM gain at 0.4 Hz was also decreased in ET compared with HCs. However, there was no significant difference of oculomotor parameters between de novo PD and ET patients. Furthermore, prolonged saccadic latency was correlated with long disease duration, whereas decreased SPEM gain was associated with severe motor symptoms in de novo PD patients. Ocular movements are impaired in de novo, drug naïve PD patients; these changes could be indicators for disease progression in PD.

1 Anu Muraja‐Murro, 1 Ari Pääkkönen, 2 Leena Jutila, 2 Reetta Kälviäinen, 3 Arto Immonen, 1 Sara Määttä, and 1 Esa Mervaala ( 1 Clinical Neurophysiology, Kuopio University Hospital, University of Kuopio, Kuopio, Finland ; 2 Neurology, Kuopio University Hospital, University of Kuopio, Kuopio, Finland ; and 3 Neurosurgery, Kuopio University Hospital, University of Kuopio, Kuopio, Finland ) Rationale: Mismatch‐negativity (MMN) is an auditory event‐related potential (ERP) produced by a deviant stimuli that occurs infrequenty among standard stimuli. MMN is thought to reflect the activation of an automatic change‐detector system that compares new auditory input with a short‐term memory trace generated by the previous auditory stimuli. MMN in human has been demonstrated from several cortical sites, but not to our knowledge from hippocampus or amygdala. This is surprising, given that these limbic structures are so essential for learning and memory functions. We could obtain MMN from these temporomesial structures using intracranial electrodes in adult patients undergoing presurgical evaluation for epilepsy surgery. Methods: 4 adults with intractable temporal lobe seizures (age 32–48 years) had each 2–4 stereotactically implanted 6‐contact depth‐electrodes at amygdalo‐hippocampal complex. The electrodes were implanted via lateral approach and their exact anatomical localizations were confirmed by MRI and CT in situ. After the post hoc anatomical localization of the depth‐electrodes, the presence of MMN could be studied from 6 hippocampi and 5 amygdalas (i.e., the electrode tips were exactly within amygdalo‐hippocampal complex). The most mesial depth‐electrode contacts were chosen for the MMN analysis with the MMN latency range of 120–250 ms, as well as with the P300 range of 250–500 ms. We analyzed possible statistically significant differences between the ERPs to deviant and standard tones. Results: A definite MMN within 120–250 ms latency range could be recorded from 4/6 hippocampi and 3/5 amygdalas. MMN was also detected within 250–500 ms latency range in 3/6 hippocampi and 2/5 amygdalas, respectively. In only one patient the hippocampal MMN resembled typical scalp‐recorded MMN. In all, the MMN decreased from the deepest contacts towards the cortex, suggesting a local maximum of MMN at the amygdalo‐hippocampal complex. Conclusions: Our data implicates that a local and early (120–500 ms post‐stimuli) automatic electrophysiological change‐detector system exists within the amygdalo‐hippocampal complex. This data is the first to demonstrate that also these temporomesial structures are activated and involved in mismatch detection, and is in line with recent sensory mismatch fMRI studies. Other sensory stimuli might also produce MMN in the same structures, possibly thus revealing a common function for hippocampus and amygdala in early sensory stimulus detection. 1 Tobias Loddenkemper, 2 Gabriel Moeddel, 1 Elia M. Pestana, 1 Deepak K. Lachhwani, 1 Ajay Gupta, 1 Prakash Kotagal, and 1 Elaine Wyllie ( 1 Department of Epilepsy and Sleep Disorder, The Cleveland Clinic Foundation, Cleveland, OH ; and 2 Department of Neurology, Universitaetsklinikum Muenster, Muenster, Westfalen, Germany ) Rationale: The intracarotid amobarbital test (IAT) is part of the presurgical workup of patients scheduled for epilepsy surgery to determine language and memory lateralization. Most information on results and complications are derived from adults. Little is known about children undergoing IAT. Difficulties arise from anxiety, need for barbiturate dosage adjustment, and impaired baseline memory in children with mental retardation [4]. The goal of this study was 1) to describe language lateralization in children with epilepsy and 2) to outline complications during IAT. Methods: 126 consecutive pediatric IAT performed at the Cleveland Clinic Foundation during a seven year period were reviewed. Results: 44 patients were age 5–12 years, 82 were age 13–18. 102 were right‐handed. Amobarbital (n = 96, average dose: 100 +‐ 25 mg) or Methohexital (n = 30, average dose 5 +‐ 1 mg) was injected into the left (n = 18), right (n = 13), or both (n = 95) ICA. Language was localized in 95 patients (75.4%): 75 [78.9%] were left, 6 [6.3%] were right, 14 [14.7%] bilateral language dominant. Neurological complications included prolonged lethargy impairing language and memory evaluation in 4 patients. Four children had a seizure after injection. Additionally, valid data could not be obtained due to fear or agitation in three children age 5–9 years. No lasting neurological deficits were seen. General complications included shortness of breath after contrast injection in one boy. One girl presented with fever of 38.5 C the night after the procedure complaining of groin pain. No other major complications were seen. Conclusions: This is one of the largest pediatric IAT series studied so far. The data on language lateralization agree with those previously reported [1, 2, 3]. The IAT in children is an invasive test with a potential for complications, as in adults, occuring in 10 out of 126 patients [7.9%]. Our series highlights the need for refinement and further development of novel methods to establish language lateralization in children during the evaluation for epilepsy surgery. REFERENCES 1. Loring D et al : . Neuropsychologia 28/8 ( 1990 ): 831 – 938 . 2. Mateer CA , Dodrill CB : . Hum Neurobiol 2 ( 1983 ): 135 – 142 3. Strauss E , Wada J : . Cortex 19 ( 1983 ): 165 – 177 ). 4. Szabo CA , Wyllie E : . Epilepsy Res 15 () ( 1993 ): 239 – 246 1 Eija Ronkainen, 1 Juha T. Korpelainen, 2 Heikki V. Huikuri, 1 Vilho V. Myllylä, and 1 Jouko I.T. Isojärvi ( 1 Department of Neurology, University of Oulu, Oulu, Finland ; and 2 Department of Internal Medicine, Division of Cardiology, University of Oulu, Oulu, Finland ) Rationale: To prospectively evaluate changes in interictal heart rate (HR) variability in patients with temporal lobe epilepsy (TLE) after 4 years follow‐up. Methods: A 24‐hour ECG recording was obtained at baseline and four years after first record

The possible relationship between essential tremor (ET) and Parkinson's disease (PD) has been controversial since the first description of PD. However, there is increasing evidence suggesting an overlap between these two disorders. The aim of this review is to examine the relationship between PD and ET, focusing on clinical, epidemiologic, genetic, neuroimaging, and neuropathological data, and the presence of cardinal parkinsonism symptoms in ET. We conducted a PubMed search for articles published between 1966 and November 2011 regarding the relationship between ET and PD and the presence of postural tremor in PD patients; the presence of rest tremor, rigidity, and slowed movements in ET patients is reviewed. Clinical series, follow-up studies of ET patients, and case-control and genetic epidemiological studies indicate that ET is associated with increased risk for PD. Some neuroimaging studies and neuropathological reports suggest an association between the two diseases. ET patients show high prevalence of rest tremor, and at least seven studies described slowed movements (possibly related to cerebellar dysfunction and/or bradykinesia) in patients with ET. There is reasonable epidemiological and clinical evidence to support a link between ET and PD, although it is not clear what factors predict ET patient risk for developing PD or, more rarely, of PD patients developing ET. Future multicentric and multidisciplinary studies including epidemiological, clinical, neuroimaging, genetic, and neuropathological assessments are required to understand these associations.

Epidermal growth factor (EGF) is a neurotrophic factor that plays an important role in Parkinson's disease (PD). We measured plasma EGF level in PD, essential tremor (ET) and normal controls to investigate whether it changes in PD and whether it is associated with motor and non-motor symptoms of PD. 100 patients with PD, 40 patients with ET as disease control and 76 healthy persons were enrolled in the present study. Motor and non-motor symptoms were assessed by different scales. Plasma EGF levels of three groups were measured by enzyme-linked immunosorbent assay kit. Spearman test and linear logistics regression model were used to test the correlation of EGF with motor and non-motor symptoms of PD. Plasma EGF level was significantly decreased in early PD patients compared with normal control, but not in advanced PD patients. Interestingly, plasma EGF level was significantly increased in advanced PD and total PD patients compared with ET patients, but not in early PD patients. In addition, plasma EGF level was correlated with UPDRS-III scores in PD. Also plasma EGF level was correlated with UPDRS-III scores and NMS scores in early PD. Our results suggested that plasma EGF decreased in the early stage of PD and increased later on in the PD disease course. Also, plasma EGF level was increased significantly in PD compared with ET patients and correlated with motor and non-motor symptoms in early PD.

Until today there is no reliable test that can clearly distinguish Parkinson's disease (PD) from the essential tremor (ET). Our aim was to determine the usefulness of the transcranial sonography (TCS) in the differential diagnosis of the PD and ET as well as the interobserver reliability for this method. Transcranial sonography of substantia nigra and clinical examination were performed on 80 PD patients, 30 ET patients, and 80 matched controls by two independent physicians. Bilateral SN hyperechogenicity over the margin of 0.20 cm(2) was found in 91% of PD patients, 10% of healthy subjects, and in 13% patients with ET. Interobserver agreement for this method was significant (Student's t-test, P = 1.000). Substantia nigra hyperechogenicity on TCS is a highly specific finding of PD, where in healthy individuals or in ET patients, it might correspond to an increased risk of developing PD later in life or might also be because of the impairment of nearby area of nucleus ruber in ET patients, as suggested by positron emission tomography studies. TCS may serve as a practical and sufficiently sensitive neuroimaging tool in PD diagnoses and in distinguishing it from ET; its repeatability and accuracy might add to its practical value.

Rapid eye movement (REM) sleep behavior disorder (RBD) occurs occasionally in essential tremor (ET), but polysomnographic REM sleep without atonia (RSWA) analyses have been sparse. To characterize the amount and distribution of polysomnographic RSWA, the electrophysiologic substrate of RBD, in patients with Parkinson's disease (PD) and ET. We analyzed quantitative RSWA in 73 patients: PD (23), ET (23), and age-sex-matched controls (27). None had dream-enactment behavior history or received antidepressants. Phasic, tonic, "any," and phasic-burst duration RSWA measures were calculated in the submentalis (SM) and anterior tibialis (AT) muscles. The automated REM atonia index (RAI) was also determined. Statistical analysis was performed by Kruskal-Wallis rank-sum and Mann-Whitney tests. SM phasic RSWA was significantly greater for PD than ET patients and controls (12.5% ± 12.8% vs. 4.9% ± 6.7%, 3.9% ± 2.6%), as was SM "any" (13.54% ± 14.30% vs. 5.2% ± 7.6%, 4.2% ± 2.6%). RAI was significantly lower in PD than in ET and controls (0.78 ± 0.23 vs. 0.92 ± 0.09 vs. 0.90 ± 0.17, P ≤ 0.005), but no different between ET and controls. AT phasic and "any" RSWA was similar between the 3 groups. ET and control RSWA was similar in all measures. Two ET patients (8.7%) had SM RSWA similar to PD patients. Elevated SM RSWA distinguished PD from ET in patients without dream-enactment symptoms and occurs frequently in PD patients, and in isolated tremor suggests underlying synucleinopathy. Prospective studies will further validate these findings.

Fragile X-associated tremor/ataxia syndrome (FXTAS), a neurodegenerative disease that affects carriers of a 55-200 CGG repeat expansion in the fragile X messenger ribonucleoprotein 1 (FMR1) gene, may be given an incorrect initial diagnosis of Parkinson's disease (PD) or essential tremor (ET) due to overlapping motor symptoms. It is critical to characterize distinct phenotypes in FXTAS compared to PD and ET to improve diagnostic accuracy. Fast as possible (FP) speed and dual-task (DT) paradigms have the potential to distinguish differences in gait performance between the three movement disorders. Therefore, we sought to compare FXTAS, PD, and ET patients using quantitative measures of functional mobility and gait under self-selected (SS) speed, FP, and DT conditions. Participants with FXTAS (n = 22), PD (n = 23), ET (n = 20), and controls (n = 20) underwent gait testing with an inertial sensor system (APDM™). An instrumented Timed Up and Go test (i-TUG) was used to measure movement transitions, and a 2-min walk test (2MWT) was used to measure gait and turn variables under SS, FP, and DT conditions, and dual-task costs (DTC) were calculated. ANOVA and multinomial logistic regression analyses were performed. PD participants had reduced stride lengths compared to FXTAS and ET participants under SS and DT conditions, longer turn duration than ET participants during the FP task, and less arm symmetry than ET participants in SS gait. They also had greater DTC for stride length and velocity compared to FXTAS participants. On the i-TUG, PD participants had reduced sit-to-stand peak velocity compared to FXTAS and ET participants. Stride length and arm symmetry index during the DT 2MWT was able to distinguish FXTAS and ET from PD, such that participants with shorter stride lengths were more likely to have a diagnosis of PD and those with greater arm asymmetry were more likely to be diagnosed with PD. No gait or i-TUG parameters distinguished FXTAS from ET participants in the regression model. This is the first quantitative study demonstrating distinct gait and functional mobility profiles in FXTAS, PD, and ET which may assist in more accurate and timely diagnosis.

The motor symptoms of Parkinson's disease (PD) are thought to result from increased inhibitory outflow from the basal ganglia to the pallidal receiving areas of thalamus (ventral oral anterior and posterior-Voa,Vop). To test this hypothesis, we examined the firing rates of neurons in pallidal and cerebellar receiving areas of thalamus in five PD patients and compared them to those of neurons in comparable regions of motor thalamus in two other patient groups where hyperactivity of GPi is not believed to occur [essential tremor (ET), pain]. Neuronal recordings were made during microelectrode-guided functional stereotactic neurosurgery. The mean spontaneous firing rate (MSFR) of neurons classified as voluntary neurons and presumed to be in pallidal receiving areas of thalamus in PD patients [7.4 +/- 1.0 (SE) Hz] was significantly lower (P < 0.01) than in the ET (18.1 +/- 3.0 Hz) and pain (19.0 +/- 1.9Hz) groups. In contrast, the MSFR of neurons classified as kinesthetic and presumed to be primarily in the cerebellar receiving area of thalamus (ventral intermediate-Vim), although some are probably in the deep shell region of the ventrocaudal nucleus (VPLa), was significantly greater in ET patients (25.8 +/- 3.5 Hz) than in the PD (14.3 +/- 1.6 Hz; P < 0.01) and pain (16.1 +/- 1.5 Hz; P < 0.05) groups. Similar findings were obtained when the neurons were grouped according to their estimated locations in Voa/Vop and Vim of motor thalamus. These data provide support for the prediction of the classical pathophysiological model of PD and moreover suggest that pathophysiology in the cerebello-thalamo-cortical pathway may be a possible cause of tremor in ET patients.

To study prevalence, specific patterns and response to treatment of tremor in dementia with Lewy bodies (DLB), in comparison with other tremulous disorders prevalence, qualitative and quantitative features of tremor were studied in an incident cohort of 67 dopaminergic treatment naive DLB, 111 Parkinson’s Disease (PD) and 34 Essential Tremor (ET) patients. Tremulous DLB patients (tDLB) were compared with tremulous PD (tPD) and ET patients and followed for 2 years. Double blind placebo-controlled acute drug challenge with l-Dopa and alcohol was performed in all ET, 24 tDLB and 27 tPD. Effects of dopaminergic chronic treatment in all tDLB and tPD patients and primidone in 8 tDLB were also assessed. Tremor occurred in 44.76 % of DLB patients. The tDLB patients presented a complex pattern of mixed tremors, characterized by rest and postural/action tremor, including walking tremor and standing overflow in 50 % tDLB. Standing tremor with overflow was characteristic of tDLB (p < 0.001). Head tremor was more frequent in tDLB than tPD and ET (p = 0.001). The tDLB tremors were reduced by acute and chronic dopaminergic treatments (p < 0.01) but not by alcohol or primidone. Tremor occurs commonly in DLB patients with a complex mixed tremor pattern which shows a significant response to acute and chronic dopaminergic treatments. Recognizing that there is a clinical category of tremulous DLB may help the differential diagnosis of tremors.Electronic supplementary materialThe online version of this article (doi:10.1007/s00415-013-6853-y) contains supplementary material, which is available to authorized users.

Indication-based analysis of patient outcomes following deep brain stimulation surgery

Objective To determine the validity of transcranial sonography (TCS) in the differential diagnosis of Parkinson's disease (PD) and essential tremor (ET). Methods TCS was performed in 100 patients with PD, 33 patients with ET and 100 normal controls in a blind manner. The echo signal intensity of the substantia nigra was classified into grade Ⅰ-Ⅴ for semi-quantitative analysis. When the echo intensity was grade Ⅲ or more, it was deemed as abnormal and the area of the substantia nigra hyperechogenicity would be measured and its ratio to the area of the whole midbrain ( S/M ) would be calculated. Results ( 1 ) Semi-quantitative analysis: the ratio of the persons whose echo intensity of the substantia nigra was grade Ⅲ or more was greater (76. 00％ ,76/100) in PD than ET (9. 09％, 3/33) and normal controls ( 13.00％, 13/100; x2 = 130. 622, P ＜0. 01 ). However, there was no difference between ET and controls. (2) Quantitative analysis: the median and quartile range of the area of substantia nigra hyperechogenicity and S/M were greater in PD patients ( O. 54 ( 0. 57 ), 11.03 ( 9. 00 ) ) than ET ( 0. 00(0.04), 0.00(1.55),H= 42.39,42.19, both P＜0. 01, respectively) and normal controls (0.00(0. 00), 0. 00 (0. 00 ), H = 121.86,121.47, both P ＜ 0. 01, respectively), and there was no difference between ET and controls. (3) Using the area of hyperechogenicity ≥0. 20 cm2 or S/M ≥ 7％ as a cut off for predicting PD, the sensitivity, specificity and accuracy were 85.39％, 78. 38％ and 81.50％ or 86. 02％,81.31％ and 83.50％ ,respectively. But there was no significant difference for the accuracy (Z = 0. 683,P ＞ 0. 05). Conclusion TCS might find the specific hyperechogenicity of substantia nigra in PD patients,providing useful information to distinguish PD from ET. Key words: Ultrasonography, doppler, transcranial; Substantia nigra; Parkinson disease; Essential tremor

Tremor was suppressed by test stimulation of the thalamic ventralis intermedius (VIM) nucleus at high frequency (130 Hz) during stereotaxy in nonanesthetized patients suffering from Parkinson's disease or essential tremor. Ventralis intermedius stimulation has since been used by the authors over the last 8 years as a treatment in 117 patients with movement disorders (80 cases of Parkinson's disease, 20 cases of essential tremor, and 17 cases of various dyskinesias and dystonias including four multiple sclerosis). Chronic electrodes were stereotactically implanted in the VIM and connected to a programmable stimulator. Results depend on the indication. In Parkinson's disease patients, tremor, but not bradykinesia and rigidity, was selectively suppressed for as long as 8 years. Administration of L-Dopa was decreased by more than 30% in 40 Parkinson's disease patients. In essential tremor patients, results were satisfactory but deteriorated with time in 18.5% of cases, mainly for patients who presented an action component of their but deteriorated with time in 18.5% of cases, mainly for patients who presented an action component of their tremor. In other types of dyskinesias (except multiple sclerosis), results were much less favorable. Fifty-nine patients underwent bilateral implantation and 14 other patients received implantation contralateral to a previous thalamotomy. Thirty-seven patients (31.6%) experienced minor side effects, which were always well tolerated and immediately reversible. Three secondary scalp infections led to temporary removal of the implanted material. There was no permanent morbidity. This tremor suppression effect could be due to the inhibition or jamming of a retroactive loop. Chronic VIM stimulation, which is reversible, adaptable, and well tolerated even by patients undergoing bilateral surgery (74 of 117 patients) and by elderly patients, should replace thalamotomy in the regular surgical treatment of parkinsonian and essential tremors.

<h3>Objective:</h3> We sought to investigate the concentrations of neurofilament light chain (NfL) in essential tremor (ET) patients and healthy controls. <h3>Background:</h3> Inquiries into the etiology, pathophysiology, and nosology of essential tremor (ET) stand to benefit from the identification of disease biomarkers. Serum neurofilament light chain (NfL) has emerged as a novel signature of conditions in which neuronal injury reflects an outcome of the ongoing disease process. <h3>Design/Methods:</h3> In this cross-sectional, case-control, observational study, 41 ET patients and 41 healthy controls underwent clinical assessments and measurement of serum NfL concentration using Simoa technology. <h3>Results:</h3> Serum NfL was elevated in ET patients (median = 16.6 pg/mL) versus controls (median = 11.3pg/mL) (p &lt;0.001). NfL concentrations remained higher in ET patients than controls after stratification by sex (p = 0.006 and 0.02, for female and male participants, respectively). This difference persisted after accounting for age, sex and Montreal Cognitive Assessment score in a multiple linear regression model (p = 0.00947, Benjamini-Hochberg correction). <h3>Conclusions:</h3> In this sample of ET patients and controls, serum NfL concentrations were significantly higher in ET. Studies in additional cohorts of ET cases would be of value in attempting to replicate these results and assessing diagnostic utility. <b>Disclosure:</b> The institution of Dr. Salinas has received research support from North Texas VA Health Care System New Investigator Award. The institution of an immediate family member of Dr. Salinas has received research support from Veterans Health Administration. Nora Hernandez has nothing to disclose. Dr. Louis has received personal compensation in the range of $500-$4,999 for serving as an Editor, Associate Editor, or Editorial Advisory Board Member for Wolters Kluwer - Merritt’s Textbook of Neurology. The institution of Dr. Louis has received research support from National Institutes of Health.