Dopamine agonist withdrawal syndrome associated factors: A retrospective chart review.

Dopamine agonist withdrawal syndrome (DAWS) has been introduced to describe the constellation of symptoms resulting from reduction or suspension of dopamine agonist medications. In patients with Parkinson's disease (PD) the impact of DAWS can be significant in terms of distress and disability. Unfortunately, no standard treatment exists other than reintroduce the dopamine agonist even in the presence of adverse effects. Therefore, identification of vulnerable patients would be beneficial. Previous studies have linked DAWS with impulse control disorder behavior (ICD), higher dopamine agonist doses, and milder motor impairment in PD patients. We conducted a retrospective chart review of PD patients treated with dopamine agonist. A total of 313 charts from January 2011 to December 2013 were reviewed, showing 126 patients who were discontinued from dopamine agonist. Twenty-one patients (16.8 %) fulfilled the diagnostic criteria for DAWS. Factors associated with the occurrence of DAWS were: (1) dose of dopamine agonist ≥150 mg expressed in levodopa equivalents daily dose (LEDD) (p = 0.018), (2) impulse control disorder as an adverse effect to dopamine agonist (p = 0.002), and (3) prior deep brain stimulation (DBS) (p = 0.049). The probability of developing DAWS in the presence of all 3 identified factors was 92 %; presence of 2 factors raised the probability up to 70 %; the presence of one factor increased the probability up to 30 %. In the absence of these 3 factors the probability of developing DAWS was 3 %. Prospective studies are warranted to confirm these findings.

Impact of behavioral side effects on the management of Parkinson patients treated with dopamine agonists.

Dopamine agonists are one of the main stay of treatment option for Parkinson disease (PD). Side effects that develop from their use are generally categorized into behavioral and non-behavioral. Behavioral side effects include: impulse control behavior disorder (ICD), psychosis and cognitive impairment. Non-behavioral side effects include: nausea/vomiting, "sleep attacks", leg swelling, weight gain and orthostasis. The aim of this study is to evaluate the clinicians' response to PD patients who developed behavioral side effects from dopamine agonists, in comparison to those patients who developed only non-behavioral side effects. We performed a retrospective chart review of all patients diagnosed with PD over a two year period. Among 313 patients who were on a dopamine agonist, 156 reported side effects. Sixty-five patients reported behavioral (with or without non-behavioral) side effects, while 91 experienced only non-behavioral side effects. Forty-nine out of the 65 patients (75.3%) who experienced behavioral side effects had their dopamine agonist dose decreased compared to 53 out of 91patients (58.2%) who experienced only non-behavioral side effects (Chi square = 4.92, p < 0.05). Patients with behavioral side effects were 3 times more likely have their dose decreased (OR = 3.3; 95%CI = 1.442-7.551; P = 0.005). However, neither taper speed nor the occurrence of dopamine agonist withdrawal syndrome (DAWS) differed between the two groups. Amongst PD patients treated with dopamine agonists, the presence of behavioral side effects independently increased the chance of dopamine agonist dose reduction. Prospective studies are needed to confirm these findings.

A Computerized Cognitive behavioral therapy Randomized, Controlled, pilot trial for insomnia in Parkinson Disease (ACCORD-PD).

BACKGROUND: Parkinson disease (PD) is associated with a high prevalence of insomnia, affecting up to 88% of patients. Pharmacotherapy studies in the literature addressing insomnia in PD reveal disappointing and inconsistent results. Cognitive behavioral therapy (CBT) is a novel treatment option with durable effects shown in primary insomnia. However, the lack of accessibility and expense can be limiting. For these reasons, computerized CBT for insomnia (CCBT-I) has been developed. The CCBT-I program is a 6-week web-based course consisting of daily "lessons" providing learnable skills and appropriate recommendations to help patients improve their sleep habits and patterns. METHODS: We conducted a single-center, pilot, randomized controlled trial comparing CCBT-I versus standardized sleep hygiene instructions to treat insomnia in PD. Twenty-eight subjects with PD experiencing insomnia, with a score > 11 on the Insomnia Severity Index (ISI) were recruited. Based on a 6-point improvement in ISI in treatment group when compared to controls and an alpha = 0.05 and beta of 0.1 (power = 90%) a sample size of 11 patients (on active treatment) were required to detect this treatment effect using a dependent sample t-test. RESULTS: In total, 8/14 (57%) subjects randomized to CCBT-I versus 13/14 (93%) subjects randomized to standard education completed the study. Among completers, the improvement in ISI scores was greater with CCBT-I as compared to standard education (-7.9 vs -3.5; p = 0.03). However, in an intention-to-treat analysis, where all enrolled subjects were included, the change in ISI between groups was not significant (-.4.5 vs -3.3; p = 0.48), likely due to the high dropout rate in the CCBT-I group (43%). CONCLUSION: This pilot study suggests that CCBT-I can be an effective treatment option for PD patients with insomnia when the course is thoroughly completed. High drop-out rate in our study shows that although effective, it may not be a generalizable option; however, larger studies are needed for further evaluation.

Dopamine agonist withdrawal syndrome (DAWS) in a tertiary Parkinson disease treatment center.

INTRODUCTION: Dopamine agonists are a mainstay of treatment for patients with Parkinson disease (PD). However, side effects limit their use, often necessitating dose change. Upon withdrawal, patients may experience dopamine agonist withdrawal syndrome (DAWS). To date, there is no established protocol for the prevention or treatment of DAWS. METHODS: We performed a retrospective chart review of PD patients who were taking a dopamine agonist. RESULTS: In our large cohort of 313 PD patients who were on a dopamine agonist, we found that 39.5% (n=124) had a change in their dose of medication for various reasons, including 102 patients who experienced a side effect on a dopamine agonist. Twenty out of 102 patients (19.6%) developed symptoms consistent with DAWS, whereas 1 out of 22 patients (4.5%) who had medication dose changed due to any other reason (e.g. dyskinesias, DBS surgery, decreased by another provider, etc.) developed symptoms consistent with DAWS. Our DAWS population had a shorter duration of PD, less exposure to a dopamine agonist, and was on a lower dose compared to those patients who did not develop DAWS. Agitation was the most common DAWS symptom reported in our cohort. Interestingly, in terms of developing DAWS, the prevalence of DAWS (19.0% vs 16.5%; p=0.76) between partial versus total discontinuation was not significantly different whether the dopamine agonist dose was decreased (21 patients) or completely stopped (103 patients). CONCLUSION: Contrary to previous reports, we have found that other side effects besides impulse control behavioral disorders also increase risk for developing DAWS. Furthermore, the prevalence of DAWS did not differ between partial versus total discontinuation of the dopamine agonist.

Rasagiline for the symptomatic treatment of fatigue in Parkinson's disease.

BACKGROUND: Fatigue affects 40% to 50% of all PD patients and is a leading cause of disability, with no clearly established or efficacious established treatments. METHODS: In this double-blinded, placebo-controlled, pilot trial, we investigated whether rasagiline improved fatigue among PD patients. Subjects were randomized to 1 mg daily of rasagiline or placebo for 12 weeks. The primary endpoint was a change in the Modified Fatigue Impact Scale from baseline to week 12. RESULTS: Thirty PD subjects (16 men), with Modified Fatigue Impact Scale baseline score of 67 ± 15, were randomized (16 to rasagiline vs. 14 to placebo). Significant improvement was noted in the mean Modified Fatigue Impact Scale score of the rasagiline group (12 points) as compared to placebo (8.5 points) from baseline to week 12 (P = 0.003). CONCLUSION: In this pilot study, rasagiline at a dose of 1 mg per day improved fatigue. Larger randomized studies are needed to confirm this finding.

Posterior spinal artery aneurysm rupture after 'Ecstasy' abuse.

Posterior spinal artery (PSA) aneurysms are a rare cause of subarachnoid hemorrhage (SAH). The commonly abused street drug 3,4-methylenedioxymethamphetamine (MDMA) or 'Ecstasy' has been linked to both systemic and neurological complications. A teenager presented with neck stiffness, headaches and nausea after ingesting 'Ecstasy'. A brain CT was negative for SAH but a CT angiogram suggested cerebral vasculitis. A lumbar puncture showed SAH but a cerebral angiogram was negative. After a spinal MR angiogram identified abnormalities on the dorsal surface of the cervical spinal cord, a spinal angiogram demonstrated a left PSA 2 mm fusiform aneurysm. The patient underwent surgery and the aneurysmal portion of the PSA was excised without postoperative neurological sequelae. 'Ecstasy' can lead to neurovascular inflammation, intracranial hemorrhage, SAH and potentially even de novo aneurysm formation and subsequent rupture. PSA aneurysms may be treated by endovascular proximal vessel occlusion or open surgical excision.

Posterior spinal artery aneurysm rupture after 'Ecstasy' abuse.

Posterior spinal artery (PSA) aneurysms are a rare cause of subarachnoid hemorrhage (SAH). The commonly abused street drug 3,4-methylenedioxymethamphetamine (MDMA) or 'Ecstasy' has been linked to both systemic and neurological complications. A teenager presented with neck stiffness, headaches and nausea after ingesting 'Ecstasy'. A brain CT was negative for SAH but a CT angiogram suggested cerebral vasculitis. A lumbar puncture showed SAH but a cerebral angiogram was negative. After a spinal MR angiogram identified abnormalities on the dorsal surface of the cervical spinal cord, a spinal angiogram demonstrated a left PSA 2 mm fusiform aneurysm. The patient underwent surgery and the aneurysmal portion of the PSA was excised without postoperative neurological sequelae. 'Ecstasy' can lead to neurovascular inflammation, intracranial hemorrhage, SAH and potentially even de novo aneurysm formation and subsequent rupture. PSA aneurysms may be treated by endovascular proximal vessel occlusion or open surgical excision.