Janis Miyasaki

Movement Disorder Society-Sponsored Revision of the Unified Parkinson's Disease Rating Scale (MDS-UPDRS): Scale Presentation and Clinimetric Testing Results

We present a clinimetric assessment of the Movement Disorder Society (MDS)‐sponsored revision of the Unified Parkinsons Disease Rating Scale (MDS‐UPDRS). The MDS‐UDPRS Task Force revised and expanded the UPDRS using recommendations from a published critique. The MDS‐UPDRS has four parts, namely, I: Non‐motor Experiences of Daily Living; II: Motor Experiences of Daily Living; III: Motor Examination; IV: Motor Complications. Twenty questions are completed by the patient/caregiver. Item‐specific instructions and an appendix of complementary additional scales are provided. Movement disorder specialists and study coordinators administered the UPDRS (55 items) and MDS‐UPDRS (65 items) to 877 English speaking (78% non‐Latino Caucasian) patients with Parkinsons disease from 39 sites. We compared the two scales using correlative techniques and factor analysis. The MDS‐UPDRS showed high internal consistency (Cronbachs alpha = 0.79–0.93 across parts) and correlated with the original UPDRS (ρ = 0.96). MDS‐UPDRS across‐part correlations ranged from 0.22 to 0.66. Reliable factor structures for each part were obtained (comparative fit index > 0.90 for each part), which support the use of sum scores for each part in preference to a total score of all parts. The combined clinimetric results of this study support the validity of the MDS‐UPDRS for rating PD.

Practice Parameter: Evaluation and treatment of depression, psychosis, and dementia in Parkinson disease (an evidence-based review): Report of the Quality Standards Subcommittee of the American Academy of Neurology

Objective: To make evidence-based treatment recommendations for patients with Parkinson disease (PD) with dementia, depression, and psychosis based on these questions: 1) What tools are effective to screen for depression, psychosis, and dementia in PD? 2) What are effective treatments for depression and psychosis in PD? 3) What are effective treatments for PD dementia or dementia with Lewy bodies (DLB)? Methods: A nine-member multispecialty committee evaluated available evidence from a structured literature review using MEDLINE, and the Cochrane Database of Health and Psychosocial Instruments from 1966 to 2004. Additional articles were identified by panel members. Results: The Beck Depression Inventory-I, Hamilton Depression Rating Scale, and Montgomery Asberg Depression Rating Scale should be considered to screen for depression in PD (Level B). The Mini-Mental State Examination and the Cambridge Cognitive Examination should be considered to screen for dementia in PD (Level B). Amitriptyline may be considered to treat depression in PD without dementia (Level C). For psychosis in PD, clozapine should be considered (Level B), quetiapine may be considered (Level C), but olanzapine should not be considered (Level B). Donepezil or rivastigmine should be considered for dementia in PD (Level B) and rivastigmine should be considered for DLB (Level B). Conclusions: Screening tools are available for depression and dementia in patients with PD, but more specific validated tools are needed. There are no widely used, validated tools for psychosis screening in Parkinson disease (PD). Clozapine successfully treats psychosis in PD. Cholinesterase inhibitors are effective treatments for dementia in PD, but improvement is modest and motor side effects may occur.Objective:To make evidence-based treatment recommendations for patients with Parkinson disease (PD) with dementia, depression, and psychosis based on these questions: 1) What tools are effective to screen for depression, psychosis, and dementia in PD? 2) What are effective treatments for depression and psychosis in PD? 3) What are effective treatments for PD dementia or dementia with Lewy bodies (DLB)? Methods:A nine-member multispecialty committee evaluated available evidence from a structured literature review using MEDLINE, and the Cochrane Database of Health and Psychosocial Instruments from 1966 to 2004. Additional articles were identified by panel members. Results:The Beck Depression Inventory-I, Hamilton Depression Rating Scale, and Montgomery Asberg Depression Rating Scale should be considered to screen for depression in PD (Level B). The Mini-Mental State Examination and the Cambridge Cognitive Examination should be considered to screen for dementia in PD (Level B). Amitriptyline may be considered to treat depression in PD without dementia (Level C). For psychosis in PD, clozapine should be considered (Level B), quetiapine may be considered (Level C), but olanzapine should not be considered (Level B). Donepezil or rivastigmine should be considered for dementia in PD (Level B) and rivastigmine should be considered for DLB (Level B). Conclusions:Screening tools are available for depression and dementia in patients with PD, but more specific validated tools are needed. There are no widely used, validated tools for psychosis screening in Parkinson disease (PD). Clozapine successfully treats psychosis in PD. Cholinesterase inhibitors are effective treatments for dementia in PD, but improvement is modest and motor side effects may occur.

Increased striatal dopamine release in Parkinsonian patients with pathological gambling: a [11C] raclopride PET study

Pathological gambling is an impulse control disorder reported in association with dopamine agonists used to treat Parkinsons disease. Although impulse control disorders are conceptualized as lying within the spectrum of addictions, little neurobiological evidence exists to support this belief. Functional imaging studies have consistently demonstrated abnormalities of dopaminergic function in patients with drug addictions, but to date no study has specifically evaluated dopaminergic function in Parkinsons disease patients with impulse control disorders. We describe results of a [(11)C] raclopride positron emission tomography (PET) study comparing dopaminergic function during gambling in Parkinsons disease patients, with and without pathological gambling, following dopamine agonists. Patients with pathological gambling demonstrated greater decreases in binding potential in the ventral striatum during gambling (13.9%) than control patients (8.1%), likely reflecting greater dopaminergic release. Ventral striatal bindings at baseline during control task were also lower in patients with pathological gambling. Although prior imaging studies suggest that abnormality in dopaminergic binding and dopamine release may be markers of vulnerability to addiction, this study presents the first evidence of these phenomena in pathological gambling. The emergence of pathological gambling in a number of Parkinsons disease patients may provide a model into the pathophysiology of this disorder.

Prevalence of repetitive and reward-seeking behaviors in Parkinson disease

We surveyed 297 patients with Parkinson disease (PD) with systematic screens and rigorous definitional criteria. Pathologic hypersexuality lifetime prevalence was 2.4%. Compulsive shopping was 0.7%. Combined with our pathologic gambling data, the lifetime prevalence of these behaviors was 6.1% and increases to 13.7% in patients on dopamine agonists.

Practice parameter: Initiation of treatment for Parkinson’s disease: An evidence-based review: Report of the Quality Standards Subcommittee of the American Academy of Neurology

In 1993, the last AAN Practice Parameter on medical treatment of Parkinson’s disease (PD) concluded that levodopa was the most effective drug for management of this disorder. Since then, a number of new compounds including non-ergot dopamine agonists (DA) and sustained-release levodopa have been released and studied. Thus, the issue of treatment in de novo PD patients warrants reexamination. Specific questions include: 1) does selegiline offer neuroprotection; 2) what is the best agent with which to initiate symptomatic treatment in de novo PD; and 3) is there a benefit of sustained release levodopa over immediate-release levodopa? Using evidence-based principles, a literature review using MEDLINE, EMBASE, and the Cochrane Library was performed to identify all human trials in de novo PD between 1966 and 1999. Only articles that fulfilled class I or class II evidence were included. Based on this review, the authors conclude: 1) Selegiline has very mild symptomatic benefit (level A, class II evidence) with no evidence for neuroprotective benefit (level U, class II evidence). 2) For PD patients requiring initiation of symptomatic therapy, either levodopa or a DA can be used (level A, class I and class II evidence). Levodopa provides superior motor benefit but is associated with a higher risk of dyskinesia. 3) No evidence was found that initiating treatment with sustained-release levodopa provides an advantage over immediate-release levodopa (level B, class II evidence).

Prospective prevalence of pathologic gambling and medication association in Parkinson disease

The authors prospectively screened 297 patients with Parkinson disease (PD), who attended a tertiary clinic, using a modified South Oaks Gambling Scale. Lifetime prevalence of pathologic gambling (PG) was 3.4% and on any dopamine agonist was 7.2%. PG was associated with earlier PD onset and with dopamine agonists but not with agonist subtype or doses. We found no association with a potent D3 receptor agonist.

Validation of the questionnaire for impulsive-compulsive disorders in Parkinson's disease.

As no comprehensive assessment instrument for impulse control disorders (ICDs) in Parkinsons disease (PD) exists, the aim of this study was to design and assess the psychometric properties of a self‐administered screening questionnaire for ICDs and other compulsive behaviors in PD. The Questionnaire for Impulsive‐Compulsive Disorders in Parkinsons Disease (QUIP) has 3 sections: Section 1 assesses four ICDs (involving gambling, sexual, buying, and eating behaviors), Section 2 other compulsive behaviors (punding, hobbyism, and walkabout), and Section 3 compulsive medication use. For validation, a convenience sample of 157 PD patients at 4 movement disorders centers first completed the QUIP, and then was administered a diagnostic interview by a trained rater blinded to the QUIP results. A shortened instrument (QUIP‐S) was then explored. The discriminant validity of the QUIP was high for each disorder or behavior (receiver operating characteristic area under the curve [ROC AUC]: gambling = 0.95, sexual behavior = 0.97, buying = 0.87, eating = 0.88, punding = 0.78, hobbyism = 0.93, walkabout = 0.79). On post hoc analysis, the QUIP‐S ICD section had similar properties (ROC AUC: gambling = 0.95, sexual behavior = 0.96, buying = 0.87, eating = 0.88). When disorders/behaviors were combined, the sensitivity of the QUIP and QUIP‐S to detect an individual with any disorder was 96 and 94%, respectively. Scores on the QUIP appear to be valid as a self‐assessment screening instrument for a range of ICDs and other compulsive behaviors that occur in PD, and a shortened version may perform as well as the full version. A positive screen should be followed by a comprehensive, clinical interview to determine the range and severity of symptoms, as well as need for clinical management.

A comparison of the mini mental state exam to the Montreal cognitive assessment in identifying cognitive deficits in Parkinson's disease.

Dementia is an important and increasingly recognized problem in Parkinsons disease (PD). The mini‐mental state examination (MMSE) often fails to detect early cognitive decline. The Montreal cognitive assessment (MoCA) is a brief tool developed to detect mild cognitive impairment that assesses a broader range of domains frequently affected in PD. The scores on the MMSE and the MoCA were compared in 88 patients with PD. A pronounced ceiling effect was observed with the MMSE but not with the MoCA. The range and standard deviation of scores was larger with the MoCA(7–30, 4.26) than with the MMSE(16–30, 2.55). The percentage of subjects scoring below a cutoff of 26/30 (used by others to detect mild cognitive impairment) was higher on the MoCA (32%) than on the MMSE (11%)(P < 0.000002). Compared to the MMSE, the MoCA may be a more sensitive tool to identify early cognitive impairment in PD.

Practice Parameter: Treatment of nonmotor symptoms of Parkinson disease Report of the Quality Standards Subcommittee of the American Academy of Neurology

Objective: Nonmotor symptoms (sleep dysfunction, sensory symptoms, autonomic dysfunction, mood disorders, and cognitive abnormalities) in Parkinson disease (PD) are a major cause of morbidity, yet are often underrecognized. This evidence-based practice parameter evaluates treatment options for the nonmotor symptoms of PD. Articles pertaining to cognitive and mood dysfunction in PD, as well as treatment of sialorrhea with botulinum toxin, were previously reviewed as part of American Academy of Neurology practice parameters and were not included here. Methods: A literature search of MEDLINE, EMBASE, and Science Citation Index was performed to identify clinical trials in patients with nonmotor symptoms of PD published between 1966 and August 2008. Articles were classified according to a 4-tiered level of evidence scheme and recommendations were based on the level of evidence. Results and Recommendations: Sildenafil citrate (50 mg) may be considered to treat erectile dysfunction in patients with Parkinson disease (PD) (Level C). Macrogol (polyethylene glycol) may be considered to treat constipation in patients with PD (Level C). The use of levodopa/carbidopa probably decreases the frequency of spontaneous nighttime leg movements, and should be considered to treat periodic limb movements of sleep in patients with PD (Level B). There is insufficient evidence to support or refute specific treatments for urinary incontinence, orthostatic hypotension, and anxiety (Level U). Future research should include concerted and interdisciplinary efforts toward finding treatments for nonmotor symptoms of PD.

Evidence Report: The efficacy and safety of mitoxantrone (Novantrone) in the treatment of multiple sclerosis: Report of the Therapeutics and Technology Assessment Subcommittee of the American Academy of Neurology

Objective: The chemotherapeutic agent mitoxantrone was approved for use in multiple sclerosis (MS) in 2000. After a review of all the available evidence, the original report of the Therapeutics and Technology Assessment Subcommittee in 2003 concluded that mitoxantrone probably reduced clinical attack rates, MRI activity, and disease progression. Subsequent reports of decreased systolic function, heart failure, and leukemia prompted the US Food and Drug Administration to institute a “black box” warning in 2005. This review was undertaken to examine the available literature on the efficacy and safety of mitoxantrone use in patients with MS since the initial report. Methods: Relevant articles were obtained through a review of the medical literature and the strength of the available evidence was graded according to the American Academy of Neurology evidence classification scheme. Results: The accumulated Class III and IV evidence suggests an increased incidence of systolic dysfunction and therapy-related acute leukemia (TRAL) with mitoxantrone therapy. Systolic dysfunction occurs in ∼12% of patients with MS treated with mitoxantrone, congestive heart failure occurs in ∼0.4%, and leukemia occurs in ∼0.8%. The number needed to harm is 8 for systolic dysfunction and 123 for TRAL. There is no new efficacy evidence that would change the recommendation from the previous report. Conclusions: The risk of systolic dysfunction and leukemia in patients treated with mitoxantrone is higher than suggested at the time of the previous report, although comprehensive postmarketing surveillance data are lacking.