Graeme MacPhee

International Multicenter Pilot Study of the First Comprehensive Self-Completed Nonmotor Symptoms Questionnaire for Parkinson's Disease: The NMSQuest Study

Nonmotor symptoms (NMS) of Parkinsons disease (PD) are not well recognized in clinical practice, either in primary or in secondary care, and are frequently missed during routine consultations. There is no single instrument (questionnaire or scale) that enables a comprehensive assessment of the range of NMS in PD both for the identification of problems and for the measurement of outcome. Against this background, a multidisciplinary group of experts, including patient group representatives, has developed an NMS screening questionnaire comprising 30 items. This instrument does not provide an overall score of disability and is not a graded or rating instrument. Instead, it is a screening tool designed to draw attention to the presence of NMS and initiate further investigation. In this article, we present the results from an international pilot study assessing feasibility, validity, and acceptability of a nonmotor questionnaire (NMSQuest). Data from 123 PD patients and 96 controls were analyzed. NMS were highly significantly more prevalent in PD compared to controls (PD NMS, median = 9.0, mean = 9.5 vs. control NMS, median = 5.5, mean = 4.0; Mann–Whitney, Kruskal–Wallis, and t test, P < 0.0001), with PD patients reporting at least 10 different NMS on average per patient. In PD, NMS were highly significantly more prevalent across all disease stages and the number of symptoms correlated significantly with advancing disease and duration of disease. Furthermore, frequently, problems such as diplopia, dribbling, apathy, blues, taste and smell problems were never previously disclosed to the health professionals.

The metric properties of a novel non-motor symptoms scale for Parkinson's disease: Results from an international pilot study

Non‐motor symptoms (NMS) in Parkinsons disease (PD) are common, significantly reduce quality of life and at present there is no validated clinical tool to assess the progress or potential response to treatment of NMS. A new 30‐item scale for the assessment of NMS in PD (NMSS) was developed. NMSS contains nine dimensions: cardiovascular, sleep/fatigue, mood/cognition, perceptual problems, attention/memory, gastrointestinal, urinary, sexual function, and miscellany. The metric attributes of this instrument were analyzed. Data from 242 patients mean age 67.2 ± 11 years, duration of disease 6.4 ± 6 years, and 57.3% male across all stages of PD were collected from the centers in Europe, USA, and Japan. The mean NMSS score was 56.5 ± 40.7, (range: 0–243) and only one declared no NMS. The scale provided 99.2% complete data for the analysis with the total score being free of floor and ceiling effect. Satisfactory scaling assumptions (multitrait scaling success rate >95% for all domains except miscellany) and internal consistency were reported for most of the domains (mean α, 0.61). Factor analysis supported the a prori nine domain structure (63% of the variance) while a small test–retest study showed satisfactory reproducibility (ICC > 0.80) for all domains except cardiovascular (ICC = 0.45). In terms of validity, the scale showed modest association with indicators of motor symptom severity and disease progression but a high correlation with other measures of NMS (NMSQuest) and health‐related quality of life measure (PDQ‐8) (both, rS = 0.70). In conclusion, NMSS can be used to assess the frequency and severity of NMS in PD patients across all stages in conjunction with the recently validated non‐motor questionnaire.

Prevalence of nonmotor symptoms in Parkinson's disease in an international setting: study using nonmotor symptoms questionnaire in 545 patients

2006, there was, no single instrument (questionnaire or scale) for attempting a comprehensive assessment of the wide range of nonmotor symptoms (NMS) of Parkinsons disease (PD). The PD nonmotor group, a multidisciplinary group of experts including patient group representatives developed and validated the NMS screening questionnaire (NMSQuest) comprising 30 items. The NMSQuest is a self completed screening tool designed to draw attention to the presence of NMS. In this paper, we present the results gathered from 545 patients using the definitive version of the NMSQuest highlighting the prevalence of the wide range of NMS flagged in the NMSQuest from consecutive PD patients in an international setting.

Correlation of Parkinson's disease severity and duration with 123I-FP-CIT SPECT striatal uptake

The variability in clinical features and the masking effects of drug therapy in Parkinsons disease (PD) can affect clinical assessment of disease severity. The aim of this study was to assess the imaging of dopamine transporters using 123I‐FP‐CIT SPECT and its correlation with disease staging, severity, and duration. Differences between the clinical severity of the onset and non‐onset side and the corresponding striatal uptake ratios were also examined. Forty‐one patients with PD (nine unilateral, 32 bilateral clinical features) were studied. Clinical severity was determined by using the Unified Parkinsons Disease Rating Score (UPDRS). Unilateral UPDRS was calculated from unilateral arm and leg resting and action tremor, rigidity, finger taps, hand movements, alternating movements, and leg agility. 123I‐FP‐CIT striatal uptake was expressed as the ratio of specific:nonspecific (SP:NS) uptake for defined brain areas. Patients with PD who had unilateral symptoms showed a significant difference between the ipsilateral and contralateral SP:NS ratios in both the caudate and putamen, but there was a considerable overlap between between the two sides. This result was repeated in patients with bilateral symptoms and there was overlap of SP:NS ratios between the two groups. For the whole group of patients with PD, striatum, caudate, and putamen SP:NS ratios correlated with disease severity assessed by UPDRS and duration of disease. The SP:NS ratios correlated with the bradykinesia subscore but not with rigidity or tremor subscore. In conclusion, this study provides further evidence that the SP:NS ratio is a robust measure of disease severity correlating with duration of PD. However, variability in uptake values suggest that factors other than nigrostriatal degeneration may contribute to disease severity. Correlation with bradykinesia but not with tremor may indicate an origin for tremor outwith the dopamine transporter system. 123I‐FP‐CIT SPECT offers significant potential in defining the nigrostriatal changes in PD.

The Nondeclaration of Nonmotor Symptoms of Parkinson's Disease to Health Care Professionals: An International Study Using the Nonmotor Symptoms Questionnaire

The nonmotor symptoms (NMS) of Parkinsons disease (PD) are less well recognised and can be more troublesome to patients and carers than classical motor features. NMS are frequently missed during routine consultations and such under‐recognition may have implications on quality of care given that many NMS are treatable. To determine the proportion of patients not declaring NMS to healthcare professional (HCP) as assessed by self completion of the NMS questionnaire (NMSQuest), a validated, self‐completing questionnaire with 30 items. Multicentre international study. The data was collected from PD patients across all age groups and stages attending outpatient clinics in specialist and care of the elderly settings. 242 patients recruited and undeclared NMS ranged from 31.8% (diplopia) to 65.2% (delusions). The most frequently nondeclared symptoms were delusions, daytime sleepiness, intense and vivid dreams, and dizziness. In many, appropriate treatments for undeclared NMS were started only after these were recognised following completion of NMSQuest. NMS of PD are frequently undeclared at routine hospital consultation and may be related to the fact that patients often do not link these symptoms with PD or may be too embarrassed to discuss these. Use of NMSQuest allows patients to flag symptoms which may be otherwise undeclared and remain untreated when potential treatments exist.

Problematic gambling on dopamine agonists: Not such a rarity.

Excessive gambling is recognized with dopamine agonist therapy, but the prevalence is unknown. We assessed the prevalence of excess gambling by specific prospective enquiry in Parkinsons disease patients attending six West Scotland movement disorder clinics. Of 388 patients taking anti‐Parkinson medication, 17 (4.4%) developed pathological gambling, all of whom were prescribed dopamine agonists. Thus, 8% of patients taking dopamine agonists had pathological gambling. Pathological gambling is not uncommon, and patients should be made aware of this potential adverse effect.

Switching from ergot to nonergot dopamine agonists in Parkinson's disease: A clinical series and five‐drug dose conversion table

Of 99 patients on ergot‐derived dopamine agonists informed about possible long‐term side effects, switching to a nonergot was undertaken in 88 (89%). There were adverse events in 26%. After 11 months, 82% were on their switch agonist and 93% were on any agonist. Switching dopamine agonists is feasible in this population.

Anticonvulsant therapy in the elderly—A need for placebo controlled trials

Epileptic seizures are common in the elderly, yet data concerning the long-term clinical course and apparent impact of anticonvulsant therapy are scant. We studied 73 consecutive elderly patients with a diagnosis of seizures [remote symptomatic (52%), acute symptomatic (23%), progressive symptomatic (10%), cryptogenic (15%)] during a median period of clinical review of 33 (range 3-72) months. Sixty-seven patients received anticonvulsant drugs, 38 phenytoin (PHT), 21 carbamazepine (CBZ), 6 sodium valproate (VPA) and 2 phenobarbitone. Six patients were untreated with drugs and three of these had no further seizures over a median review period of 26 months. Forty-one (61%) treated patients remained seizure free and a further nine patients suffered less than three fits per year. Seventeen patients had poorer control (three to five seizures per year in six patients and more than five seizures per year in eleven patients). Mean daily dosage of anticonvulsants (PHT 248 mg, CBZ 320 mg, VPA 571 mg) and serum concentrations were modest. Anticonvulsant side effects were reported by 27% of all treated patients (22% of those who were seizure free). Both adverse effects and satisfactory seizure control were associated in the majority of patients with serum anticonvulsant concentrations at the lower limit or below recommended therapeutic ranges utilised in the young. This study suggests that placebo controlled studies are warranted to appraise the extent to which anticonvulsant drugs modify a generally favourable prognosis for seizure disorders in the elderly and to adequately define the benefit-risk ratio of such drugs.

Pathological Gambling Amongst Parkinson's Disease and ALS Patients in an Online Community (PatientsLikeMe.com)

Pathological gambling (PG) has been identified in Parkinsons disease (PD), but such gambling behaviors may also occur in amyotrophic lateral sclerosis (ALS). We sought to estimate the prevalence of PG amongst members of a web‐based community, PatientsLikeMe.com. A survey was constructed, consisting of demographic information, the South Oaks Gambling Screen (SOGS), the K‐6 measure of distress, and items related to motivation for gambling. Data were obtained from 236 ALS patients and 208 PD patients. Of the PD patients, 13% were classified as problem gamblers compared with 3% of ALS patients (χ2 = 14.005, P ≤ 0.001). PD patients reported thoughts about gambling to be more distressing, harder to resist and more outside their control than ALS patients. Thus, the higher prevalence of compulsive behavior in PD may relate to damaged reward pathways or medication rather than to the effects of living with a chronic progressive neurological disorder per se.

Prescription of drugs with potential adverse effects on cardiac conduction in Parkinson's disease

BACKGROUND Epidemiological studies report an association of ventricular arrhythmias with medication through prolongation of the cardiac QT interval. This has implications in the management of Parkinsons disease, as commonly prescribed drugs for non-motor symptoms and comorbidities have QT prolonging potential. OBJECTIVES To review prescribed medication in Parkinsons disease patients, in particular the use of drugs that may prolong the cardiac QT interval, in relation to other risk factors for QT prolongation. METHODS Medication prescription and doses, presence of underlying cardiac disease, patient age, and sex were recorded in a cross-sectional sample of 360 current PD patients attending two district and one regional specialist hospital-based movement disorder clinics. RESULTS We sampled 360 consecutive patients with PD, median age 66.5 years (interquartile range 58.5-74.8) and median disease duration 4.2 years (interquartile range 1.2-8.0 years). 125 (34.7%) were taking one or more drugs with definite potential to prolong QT, including domperidone in 91 (25.2%), citalopram or escitalopram in 47 (13.1%), and concurrent antibiotics in 5 (1.3%). Cofactors increasing the risk for QT interval prolongation were: age over 60 years 71.7%, female sex 46.9%, and presence of cardiac disease 19.2%. In patients with combined risk factors, the rate of prescription of at least one definite QT prolonging drug was between 34.5 and 42.1%. CONCLUSIONS Combination therapy and comorbidity relevant to cardiac QT prolongation are common in patients with Parkinsons disease. Strategies to reduce the proportion of patients at risk from iatrogenic adverse cardiac events are warranted.