Clinical profiles and outcomes of deep brain stimulation in G2019S LRRK2 Parkinson disease

OBJECTIVE The objective of this study was to evaluate clinical features and response to deep brain stimulation (DBS) in G2019S LRRK2-Parkinson disease (LRRK2-PD) and idiopathic PD (IPD). METHODS The authors conducted a clinic-based cohort study of PD patients recruited from the Mount Sinai Beth Israel Genetics database of PD studies. The cohort included 87 participants with LRRK2-PD (13 who underwent DBS) and 14 DBS participants with IPD enrolled between 2009 and 2017. The baseline clinical features, including motor ratings and levodopa-equivalent daily dose (LEDD), were compared among LRRK2-PD patients with and without DBS, between LRRK2-PD with DBS and IPD with DBS, and between LRRK2-PD with subthalamic nucleus (STN) and internal segment of the globus pallidus (GPi) DBS. Longitudinal motor scores (Unified Parkinson’s Disease Rating Scale–part III) and medication usage were also assessed pre- and postoperatively. RESULTS Compared to LRRK2-PD without DBS (n = 74), the LRRK2-PD with DBS cohort (n = 13) had a significantly younger age of onset, longer disease duration, were more likely to have dyskinesia, and were less likely to experience hand tremor at disease onset. LRRK2-PD participants were also more likely to be referred for surgery because of severe dyskinesia (11/13 [85%] vs 6/14 [43%], p = 0.04) and were less likely to be referred for medically refractory tremor (0/13 [0%] vs 6/14 [43%], p = 0.02) than were IPD patients. Among LRRK2-PD patients, both STN-DBS and GPi-DBS targets were effective, although the sample size was small for both groups. There were no revisions or adverse effects reported in the GPi-DBS group, while 2 of the LRRK2-PD participants who underwent STN-DBS required revisions and a third reported depression as a stimulation-related side effect. Medication reduction favored the STN group. CONCLUSIONS The LRRK2-PD cohort referred for DBS had a slightly different profile, including earlier age of onset and dyskinesia. Both the STN and GPi DBS targets were effective in symptom suppression. Patients with G2019S LRRK2 PD were well-suited for DBS therapy and had favorable motor outcomes regardless of the DBS target. LRRK2-DBS patients had longer disease durations and tended to have more dyskinesia. Dyskinesia commonly served as the trigger for DBS surgical candidacy. Medication-refractory tremor was not a common indication for surgery in the LRRK2 cohort.

A Case Report of Essential Tremors Treated with Yeokhan-san

Objective: This report describes the case of a patient with essential tremors of the mouth and hands, which were improved by Yeokhan-san treatment.Methods: To relieve the symptoms, Korean medicine treatments, including Yeokhan-san, Ohaeng-Hwa acupuncture, and electronic moxibustion, were performed. To evaluate the effects of the treatments, the visual analog scale and Fahn-Tolosa-Marin clinical rating scale for tremor were used.Results: After the treatment, the patient's clinical symptoms were improved. The visual analog scale score decreased from 10 to 2 for the hand tremor and from 10 to 1 for the mouth tremor. The Fahn-Tolosa-Marin tremor scores decreased from 3 to 1 for both the hand and mouth tremors.Conclusions: The present case suggests that Yeokhan-san and Ohaeng-Hwa acupuncture are effective for the treatment of essential tremor.

Active tremor control in human-like hand tremor using fuzzy logic

<span>Tremor<span>is the vibration in sinusoidal orientation that is experienced regularly by a person with Parkinson’s disease (PD), which disturbs their daily activities. One solution that may be used to counter this tremor effect is by developing an active tremor control system in LabVIEW for linear voice coil actuator (LVCA), where the system uses proportional (P) controller and various types of fuzzy logic controller (FLC) as a hybrid controller to reduce tremor vibration. From this research, it can be concluded that the best controller for tremor reduction is the P+FLC 1^st set of rules, compared to P+FLC 2^nd set of rules, and P controller only, with the highest percentage of 88.39% of tremor reduction with the actual tremor vibration of PD patients as the reference result. The P+FLC 2^nd set of rules has the highest percentage of tremor reduction with a value of 86.81%, whereas P controller only has the highest tremor reduction percentage of 67.10%. This percentage of tremor reduction is based on the power spectral density (PSD) values, in which it represents the intensity of the tremor vibration. This experimental study can be used as an initial step for researchers and engineers to design and develop an anti-tremor device in the future.</span></span>

Unilateral loss of the swallow tail sign in a patient with idiopathic Parkinson’s disease

A 66-year-old man with underlying hypertension and dyslipidemia presented with left hand tremor for one year. He also noticed difficulty in initiating movement and slowness in activities of daily living. On examination, he was noted to have mask-like facies with reduced blinking and monotonous speech. There was presence of resting pill-rolling tremor, bradykinesia, and cogwheel rigidity which was worst on the left upper limb. Gait assessment revealed difficulty in standing up, shuffling gait with reduced arm swing which was more prominent on the left side, and turning in numbers. No cerebellar signs and supranuclear palsy were present to suggest Parkinson-plus syndrome. Susceptibility weighted imaging (SWI) showed loss of the swallow tail sign on the right side [Figure 1]. The clinical presentation, supplemented by the imaging findings were concluded to be pathognomonic of idiopathic Parkinson’s disease (IPD), Hoehn & Yahr stage 1. He was started on levodopa and benserazide twice daily with improvement of symptoms.The nigrosomes are primary subregions of the substantia nigra where dopaminergic cells are lost in IPD. Within these nigrosomes, maximal cell loss occurs in nigrosome-1; the largest subgroup of nigrosomes. Normally, they appear as a SWI-hyperintense area surrounded by hypointensity within the dorsolateral substantia nigra, akin to a swallow’s tail. In one study, poor visualization of nigrosome-1 was significantly associated with higher motor asymmetry in the contralateral side (sensitivity 98.5%, specificity 93.6%, positive-predictive value 98.3%, negative-predictive value 98.3% and an accuracy of 96%) [1]. Noh et al [2] showed that abnormality involving nigrosome-1 can be detected at 3T MR imaging with an accuracy of 94.6%. Due to the difficulty in diagnosis of early stage IPD, a loss of the swallow tail sign serves as a useful imaging biomarker to supplement the clinical diagnosis, as seen in our patient.

Correlation of visual area with tremor improvement after MRgFUS thalamotomy in Parkinson’s disease

OBJECTIVE MRI-guided focused ultrasound (MRgFUS) thalamotomy is a novel and minimally invasive alternative for medication-refractory tremor in Parkinson’s disease (PD). However, the impact of MRgFUS thalamotomy on spontaneous neuronal activity in PD remains unclear. The purpose of the current study was to evaluate the effects of MRgFUS thalamotomy on local fluctuations in neuronal activity as measured by the fractional amplitude of low-frequency fluctuations (fALFF) in patients with PD. METHODS Participants with PD undergoing MRgFUS thalamotomy were recruited. Tremor scores were assessed before and 3 and 12 months after treatment using the Clinical Rating Scale for Tremor. MRI data were collected before and 1 day, 1 week, 1 month, 3 months, and 12 months after thalamotomy. The fALFF was calculated. A whole-brain voxel-wise paired t-test was used to identify significant changes in fALFF at 12 months after treatment compared to baseline. Then fALFF in the regions with significant differences were extracted from fALFF maps of patients for further one-way repeated-measures ANOVA to investigate its dynamic alterations. The association between fALFF changes induced by thalamotomy and tremor improvement were evaluated using the nonparametric Spearman rank test. RESULTS Nine participants with PD (mean age ± SD 64.7 ± 6.1 years, 8 males) were evaluated. Voxel-based analysis showed that fALFF in the left occipital cortex (Brodmann area 17 [BA17]) significantly decreased at 12 months after thalamotomy compared to baseline (voxel p < 0.001, cluster p < 0.05 family-wise error [FWE] corrected). At baseline, fALFF in the left occipital BA17 in patients was elevated compared with that in 9 age- and gender-matched healthy subjects (p < 0.05). Longitudinal analysis displayed the dynamic changes of fALFF in this region (F (5,40) = 3.61, p = 0.009). There was a significant positive correlation between the falling trend in fALFF in the left occipital BA17 and hand tremor improvement after treatment over 3 time points (Spearman’s rho = 0.44, p = 0.02). CONCLUSIONS The present study investigated the impact of MRgFUS ventral intermediate nucleus thalamotomy on spontaneous neural activity in medication-refractory tremor-dominant PD. The visual area is, for the first time, reported as relevant to tremor improvement in PD after MRgFUS thalamotomy, suggesting a distant effect of MRgFUS thalamotomy and the involvement of specific visuomotor networks in tremor control in PD.

Towards Essential Hand Tremor Suppression via Pneumatic Artificial Muscles

Essential tremor (ET) is one of the most common movement disorders and can occur unexpectedly and develop indefinitely to any population unit. According to the recorded statistics of people suffering from ET, the disorder affects 5% of people worldwide, thus creating an ever-increasing need to investigate ways for its suppression and treatment. In this article, we investigate the capability of Pneumatic Artificial Muscles (PAMs) to reduce or even suppress ET leading to the relief of the sufferers. In our work, we designed and constructed two iterations of a glovelike setup and attempted to explore the possibility of suppressing ET on different parts of the hand by exerting force on the index finger and metacarpal region. For both glove iterations, we established an experimental protocol based on the adjustment of a force controller. Finally, we evaluated exhaustively the performance of our setup under multiple motion scenarios with the participation of an ET-diagnosed volunteer.