Istradefylline for Restless Legs Syndrome Associated with Parkinson’s Disease

Restless legs syndrome (RLS) is the most common movement disorder and is characterized by the feeling of an urgent need to move the legs while lying down or resting. RLS worsens during the evening and at night and is relieved by leg movement.1,2 It is also known that RLS is commonly comorbid with Parkinson’s disease (PD).3 Although the exact pathological mechanism of RLS is unknown, dopaminergic medications for PD, such as levodopa and other dopamine agonists, symptomatically improve RLS as well.4 Istradefylline is a highly selective adenosine A2A receptor antagonist that is thought to modulate the overactivated striatopallidal pathway (indirect pathway) in PD,4 reducing the duration of the ‘‘off’’ state and extending the ‘‘on’’ state without inducing dyskinesia.5 Istradefylline has been recently approved in Japan for the treatment of PD, but, to date, there are no data on the effect of istradefylline on RLS in PD. Here we report the cases of three patients with RLS comorbid with PD who were treated with istradefylline

The Frequency of Nonmotor Symptoms among Advanced Parkinson Patients May Depend on Instrument Used for Assessment

Background. Nonmotor symptoms (NMS) of Parkinson's disease (PD) may be more debilitating than motor symptoms. The purpose of this study was to determine the frequency and corecognition of NMS among our advanced PD cohort (patients considered for deep brain stimulation (DBS)) and caregivers. Methods. NMS-Questionnaire (NMS-Q), a self-administered screening questionnaire, and NMS Assessment-Scale (NMS-S), a clinician-administered scale, were administered to PD patients and caregivers. Results. We enrolled 33 PD patients (23 males, 10 females) and caregivers. The most frequent NMS among patients using NMS-Q were gastrointestinal (87.9%), sleep (84.9%), and urinary (72.7%), while the most frequent symptoms using NMS-S were sleep (90.9%), gastrointestinal (75.8%), and mood (75.8%). Patient/caregiver scoring correlations for NMS-Q and NMS-S were 0.670 (P < 0.0001) and 0.527 (P = 0.0016), respectively. Conclusion The frequency of NMS among advanced PD patients and correlation between patients and caregivers varied with the instrument used. The overall correlation between patient and caregiver was greater with NMS-Q than NMS-S

Effect of Deep Brain Stimulation on Parkinson's Nonmotor Symptoms following Unilateral DBS: A Pilot Study

Parkinson's disease (PD) management has traditionally focused largely on motor symptoms. Deep brain stimulation (DBS) of the subthalamic nucleus (STN) and globus pallidus internus (GPi) are effective treatments for motor symptoms. Nonmotor symptoms (NMSs) may also profoundly affect the quality of life. The purpose of this pilot study was to evaluate NMS changes pre- and post-DBS utilizing two recently developed questionnaires. Methods. NMS-Q (questionnaire) and NMS-S (scale) were administered to PD patients before/after unilateral DBS (STN/GPi targets). Results. Ten PD patients (9 STN implants, 1 GPi implant) were included. The three most frequent NMS symptoms identified utilizing NMS-Q in pre-surgical patients were gastrointestinal (100%), sleep (100%), and urinary (90%). NMS sleep subscore significantly decreased (−1.6 points ± 1.8, P = 0.03). The three most frequent NMS symptoms identified in pre-surgical patients using NMS-S were gastrointestinal (90%), mood (80%), and cardiovascular (80%). The largest mean decrease of NMS scores was seen in miscellaneous symptoms (pain, anosmia, weight change, and sweating) (−7 points ± 8.7), and cardiovascular/falls (−1.9, P = 0.02). Conclusion. Non-motor symptoms improved on two separate questionnaires following unilateral DBS for PD. Future studies are needed to confirm these findings and determine their clinical significance as well as to examine the strengths/weaknesses of each questionnaire/scale

Subthalamic deep brain stimulation in Parkinson's disease with SNCA mutations: Based on the follow-up to 10 years

Backgrounds: Although the short-term efficacy of bilateral subthalamic deep brain stimulation (DBS) has been reported in a limited number of Parkinson's disease (PD) patients with SNCA mutations, there are no data for long-term outcome. Methods: This multicenter retrospective study investigated previously reported PD patients with SNCA mutations, implanted with bilateral subthalamic DBS. We compared demographic and clinical data at baseline and last follow-up. Clinical data of motor and nonmotor symptoms and motor fluctuation were collected up to 10 years from DBS surgery. Results: Among four subjects, three had SNCA duplication and one had c.158C.A (p.A53E) mutation. The mean post-implantation follow-up duration was 5.4 +/- 3.7 years. All patients with SNCA duplication showed favorable outcome, although one died from breast cancer 1.5 years after DBS. The patient with the missense mutation became wheelchair-bound due to progressed axial, cognitive and psychiatric symptoms after 3.5 years from DBS despite the benefit on motor fluctuation. Conclusion: Based on findings in our small cohort, subthalamic DBS could be beneficial for motor fluctuation in PD patients with SNCA mutations, especially those with SNCA duplication, and cognitive and psychiatric symptoms are important for the long-term outcome of subthalamic DBS.</p

An International Survey of Deep Brain Stimulation Utilization in Asia and Oceania: The DBS Think Tank East.

Introduction: To evaluate the current utilization and challenges in fully implementing the use of deep brain stimulation (DBS) treatment in Asia and Oceania. Methods: We conducted a medical literature search to identify DBS research performed by investigators with a primary affiliation in Asian and Oceania countries between March 1, 2013, and March 1, 2019, followed by an international survey-based study. Additionally, we obtained added information regarding the DBS challenges and opportunities from the technology/industry perspective within China and Japan. We also described the current situation of DBS in India. Results: Most publications (390/494; 78.95%) in the English language originated from East Asia. In West Asia, Turkey, Israel, and Iran accounted for most DBS publications. We found no publications from the remaining 35 Asian countries. Lack of community referrals to tertiary centers was identified as the most common limitation for the widespread use of DBS in Asia (68.97%). In China, despite an increasing number of centers performing DBS surgeries, most of them accomplished less than 10 cases per year. In contrast, the number of DBS cases in Japan has been decreasing. Centers offering DBS surgeries as well as corresponding fellowship training in India are limited. Conclusion: Appropriate referrals, access, infrastructure, and the presence of full multidisciplinary DBS teams are common limitations of DBS in Asia. Most centers in China, Japan, and India performed less than 10 cases per year and a future study is expected to address the impact on quality in centers performing such few cases

Effects of STN and GPi Deep Brain Stimulation on Impulse Control Disorders and Dopamine Dysregulation Syndrome

Impulse control disorders (ICDs) and dopamine dysregulation syndrome (DDS) are important behavioral problems that affect a subpopulation of patients with Parkinson's disease (PD) and typically result in markedly diminished quality of life for patients and their caregivers. We aimed to investigate the effects of subthalamic nucleus (STN) and internal globus pallidus (GPi) deep brain stimulation (DBS) on ICD/DDS frequency and dopaminergic medication usage.A retrospective chart review was performed on 159 individuals who underwent unilateral or bilateral PD DBS surgery in either STN or GPi. According to published criteria, pre- and post-operative records were reviewed to categorize patients both pre- and post-operatively as having ICD, DDS, both ICD and DDS, or neither ICD nor DDS. Group differences in patient demographics, clinical presentations, levodopa equivalent dose (LED), and change in diagnosis following unilateral/bilateral by brain target (STN or GPi DBS placement) were examined.28 patients met diagnostic criteria for ICD or DDS pre- or post-operatively. ICD or DDS classification did not differ by GPi or STN target stimulation. There was no change in DDS diagnosis after unilateral or bilateral stimulation. For ICD, diagnosis resolved in 2 of 7 individuals after unilateral or bilateral DBS. Post-operative development of these syndromes was significant; 17 patients developed ICD diagnoses post-operatively with 2 patients with pre-operative ICD developing DDS post-operatively.Unilateral or bilateral DBS did not significantly treat DDS or ICD in our sample, even though a few cases of ICD resolved post-operatively. Rather, our study provides preliminary evidence that DDS and ICD diagnoses may emerge following DBS surgery

Paroxysmal Kinesigenic Dyskinesia-like Symptoms in a Patient with Tourette Syndrome

Background: Paroxysmal kinesigenic dyskinesia (PKD) is characterized by episodic dystonia or choreiform movements provoked by sudden voluntary movement. PKD is not commonly reported in Tourette syndrome (TS). We describe a unique case of TS with PKD-like episodic dyskinesia that responded to carbamazepine. Case Report: A 36-year-old male with long-standing TS developed paroxysmal &ldquo;cramping&rdquo;. Attacks were provoked by quick, sudden arm movements, which induced dystonic cramping, or by reaching overhead, which caused painful contraction of truncal muscles. The spells typically lasted 5&ndash;20 seconds and occurred multiple times daily. The patient&rsquo;s mother suffered from intermittent dystonic toe curling. In view of the similarity of symptoms to PKD, carbamazepine was prescribed at 400 mg daily. The symptoms resolved completely. Inadvertent discontinuation led to relapse, and resumption led to recapture of benefit. Discussion: This case demonstrates the possibility that PKD-like symptoms may co-occur with TS and may be responsive to carbamazepine.</p

Pilot feasibility study of a semi-automated three-dimensional scoring system for cervical dystonia.

The objective of this study is to test the feasibility of a semi-automated scoring system for the Toronto Western Spasmodic Torticollis Scale (TWSTRS) severity scale in patients with cervical dystonia. The TWSTRS requires training and experience. We previously developed a system to measure neck angle by analyzing three-dimensional position, obtained using Kinect, a marker-less three-dimensional depth sensor. The system can track patients' faces and bodies, automatically analyze neck angles, and semi-automatically calculate the TWSTRS severity scale score. We compared the TWSTRS severity scale scores calculated by the system with the video-based scores calculated by a neurologist trained in movement disorders. A correlation coefficient analysis was then conducted. Absolute accuracy was measured using intra-class correlation (ICC) (3,1), with 95% limits of agreement. To analyze the subscales, Cohen's kappa coefficient (κ) was calculated. A p-value of < .05 was considered statistically significant. Thirty patients were enrolled. Their average age was 52.3±16.0 years, and the male to female ratio was 3:2. The average disease duration was 11.3±12.7 years. Total score measurements by the system were significantly correlated with those rated by the movement disorder-trained neurologist (r = .596, p < .05). There was a significant correlation (r = .655, p < .05) with regard to the automated part of the scale. An adequate ICC (3,1) of .562 was obtained for total severity score (p < .001, 95% confidence interval [CI]: .259-.765), while the equivalent score was .617 for the total automated part (p < .001, 95% CI .336-.798). Our three-dimensional motion capture system, which can measure head angles and semi-automatically calculate the TWSTRS severity scale score utilizing a single-depth camera, demonstrated adequate validity and reliability. This low-cost and portable system could be applied by general practitioners treating cervical dystonia to obtain objective measurements

Cerebral microbleeds and blood pressure abnormalities in Parkinson's disease

Blood pressure abnormalities are frequently observed in patients with Parkinson's disease (PD), and are associated with cerebrovascular diseases such as white matter hyperintensities and carotid atherosclerosis. We assessed the relationship between blood pressure abnormalities and cerebral microbleeds (CMBs), a marker of cerebral small vessel disease, in 128 patients with PD. We examined supine and orthostatic blood pressures and used 24-hour ambulatory blood pressure monitoring to assess the presence or absence of orthostatic hypotension (OH), supine hypertension (SH), nocturnal hypertension (NH), and loss of nocturnal blood pressure dips (non-dipping). CMBs were found in 13 (10.2%) patients, and the median number of CMBs was 1 (range: 1 to 10). Six of these patients had deep or infratentorial CMBs, six had strictly lobar CMBs, and one had mixed CMBs. Linear regression analysis indicated that presence of both OH and SH was independently associated with greater numbers of CMBs in deep or infratentorial regions, independent of age, sex, cardiovascular risk factors, and white matter hyperintensities. NH and non-dipping were not associated with CMBs in deep or infratentorial regions, and there was no association between blood pressure and CMBs in lobar regions. Our results suggest that the presence of both OH and SH may be related to deep or infratentorial CMBs in patients with PD. Keywords: Autonomic dysfunction, Cerebral microbleeds, Orthostatic hypotension, Parkinson's disease, Supine hypertensio

Brittle Dyskinesia Following STN but not GPi Deep Brain Stimulation

Background: The aim was to describe the prevalence and characteristics of difficult to manage dyskinesia associated with subthalamic nucleus (STN) deep brain stimulation (DBS). A small subset of STN DBS patients experience troublesome dyskinesia despite optimal programming and medication adjustments. This group of patients has been referred to by some practitioners as brittle STN DBS‐induced dyskinesia, drawing on comparisons with brittle diabetics experiencing severe blood sugar regulation issues and on a single description by McLellan in 1982. We sought to describe, and also to investigate how often the &ldquo;brittle&rdquo; phenomenon occurs in a relatively large DBS practice.Methods: An Institutional Review Board‐approved patient database was reviewed, and all STN and globus pallidus internus (GPi) DBS patients who had surgery at the University of Florida from July 2002 to July 2012 were extracted for analysis.Results:&nbsp;There were 179 total STN DBS patients and, of those, four STN DBS (2.2%) cases were identified as having dyskinesia that could not be managed without the induction of an &ldquo;off state,&rdquo; or by the precipitation of a severe dyskinesia despite vigorous stimulation and medication adjustments. Of 75 GPi DBS cases reviewed, none (0%) was identified as having brittle dyskinesia. One STN DBS patient was successfully rescued by bilateral GPi DBS.Discussion: Understanding the potential risk factors for postoperative troublesome and brittle dyskinesia may have an impact on the initial surgical target selection (STN vs. GPI) in DBS therapy. Rescue GPi DBS therapy may be a viable treatment option, though more cases will be required to verify this observation.</p