Parkinson Disease: Sethi K

Olanow CW, Stern MB, Sethi K. · Department of Neurology, Mount Sinai School of Medicine, 1 Gustave Levy Place, Annenberg 14-94, New York, NY 10029, USA. · Neurology. · Pubmed #19470958 No free full text.

Abstract: Parkinson disease (PD) is an age-related neurodegenerative disorder that affects as many as 1-2% of persons aged 60 years and older. With the aging of the population, the frequency of PD is expected to increase dramatically in the coming decades. Current therapy is largely based on a dopamine replacement strategy, primarily using the dopamine precursor levodopa. However, chronic treatment is associated with the development of motor complications, and the disease is inexorably progressive. Further, advancing disease is associated with the emergence of features such as freezing, falling, and dementia which are not adequately controlled with dopaminergic therapies. Indeed, it is now appreciated that these nondopaminergic features are common and the major source of disability for patients with advanced disease. Many different therapeutic agents and treatment strategies have been evaluated over the past several years to try and address these unmet medical needs, and many promising approaches are currently being tested in the laboratory and in the clinic. As a result, there are now many new therapies and strategic approaches available for the treatment of the different stages of PD, with which the treating physician must be familiar in order to provide patients with optimal care. This monograph provides an overview of the management of PD patients, with an emphasis on pathophysiology, and the results of recent clinical trials. It is intended to provide physicians with an understanding of the different treatment options that are available for managing the different stages of the disease and the scientific rationale of the different approaches.

Simuni T, Sethi K. · Department of Neurology, Northwestern University, Chicago, IL, USA. · Ann Neurol. · Pubmed #19127582 No free full text.

Abstract: Parkinson's disease (PD) is the second most common neurodegenerative disease after Alzheimer's disease. Traditionally, attention has focused on the motor symptomatology of PD, but it is now appreciated that the nonmotor symptoms affecting neuropsychiatric, sleep, autonomic, and sensory domains occur in up to 88% of PD patients and can be an important source of disability. Nonmotor manifestations of PD play a significant role in the impairment of disease-related quality of life. The cause of nonmotor manifestations of PD is multifactorial, but to a large extent, these manifestations are related to the nature of the neurodegenerative process and the widespread nondopaminergic neuropathological changes associated with the disease. Recognition of nonmotor disability is essential not only for ascertaining the functional status of patients but also for better appreciating the nature of the neurodegenerative process in PD. In addition, a number of nonmotor manifestations can precede the onset of motor symptoms in PD and can be used as screening tools allowing for early disease identification and for trials of possible disease-modifying interventions. This article reviews depression, sleep, and autonomic dysfunction in PD.

Sethi K. · Medical College of Georgia, Augusta, Georgia, USA. · Mov Disord. · Pubmed #18781679 No free full text.

Abstract: Levodopa has been the mainstay of symptomatic therapy for Parkinson Disease (PD) for 40 years providing benefit to virtually all patients. Levodopa therapy results in improved activities of daily living, enhanced quality of life, and improved mortality. However, the long-term use of levodopa is associated with the development of motor fluctuations and dyskinesia. In addition, levodopa therapy has further limitations. It has little or no effect on certain motor features (e.g. gait and balance dysfunction) and a non-motor symptom complex (autonomic dysfunction, pain syndromes, sleep disorders, mood disturbances, dementia). Further, multiple case reports illustrate the potential of levodopa and other dopaminergic agents to cause or reveal a series of impulse control disorders. This review highlights the levodopa unresponsive symptoms in PD.

Chaudhuri KR, Martinez-Martin P, Brown RG, Sethi K, Stocchi F, Odin P, Ondo W, Abe K, Macphee G, Macmahon D, Barone P, Rabey M, Forbes A, Breen K, Tluk S, Naidu Y, Olanow W, Williams AJ, Thomas S, Rye D, Tsuboi Y, Hand A, Schapira AH. · National Parkinson Foundation Centre of Excellence, Kings College Hospital, London, United Kingdom. · Mov Disord. · Pubmed #17674410 No free full text.

Abstract: Non-motor symptoms (NMS) in Parkinson's 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 alpha, 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.

Martinez-Martin P, Schapira AH, Stocchi F, Sethi K, Odin P, MacPhee G, Brown RG, Naidu Y, Clayton L, Abe K, Tsuboi Y, MacMahon D, Barone P, Rabey M, Bonuccelli U, Forbes A, Breen K, Tluk S, Olanow CW, Thomas S, Rye D, Hand A, Williams AJ, Ondo W, Chaudhuri KR. · Unit of Neuroepidemiology, National Center for Epidemiology, Carlos III Institute of Health, Madrid, Spain. · Mov Disord. · Pubmed #17546669 No free full text.

Abstract: 2006, there was, no single instrument (questionnaire or scale) for attempting a comprehensive assessment of the wide range of nonmotor symptoms (NMS) of Parkinson's 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.

Stacy M, Hauser R, Oertel W, Schapira A, Sethi K, Stocchi F, Tolosa E. · Division of Neurology, Duke University Medical School, Durham, North Carolina 27705, USA. · Clin Neuropharmacol. · Pubmed #17095894 No free full text.

Abstract: We have previously reported that the use of a 32-symptom Wearing-off Questionnaire (WOQ-32) identified wearing off more frequently than a clinician's evaluation or the complications subscale of the Unified Parkinson Disease Rating Scale (UPDRS). However, this prototype tool was not designed for clinical practice and required simplification for daily use. Although wearing off is a commonly understood concept among neurologists caring for Parkinson disease patients, there are a number of definitions in the literature. For the purpose of this study and to include both motor and nonmotor parkinsonian symptoms, wearing off was defined as a generally predictable recurrence of motor and nonmotor symptoms that precedes scheduled doses of anti-parkinsonian medication and usually improves after those doses. Using this definition, retrospective analysis and expert opinion were used to identify the 9 most predictive and relevant of the symptoms previously identified as part of the WOQ-32. The resulting 9-symptom questionnaire (WOQ-9) identified 158 (95.8%) of the 165 subjects captured by the 32-Symptom Wearing-off Questionnaire as having wearing off, excluding 7 subjects reporting only balance difficulty (n = 3), numbness (n = 2), difficulty standing (n = 1), and abdominal discomfort (n = 1). Subjects reporting wearing off with the WOQ-9 were significantly younger, had been longer diagnosed with Parkinson disease, experienced a longer duration of levodopa therapy, exhibited a higher UPDRS total score, had higher levodopa equivalent dosages, and increased dyskinesia compared with patients not identified as wearing off with the WOQ-9. No statistical differences were noted with respect to sex, UPDRS subsection scores, Schwab & England Scale, or Hoehn & Yahr Scale.

Chaudhuri KR, Martinez-Martin P, Schapira AH, Stocchi F, Sethi K, Odin P, Brown RG, Koller W, Barone P, MacPhee G, Kelly L, Rabey M, MacMahon D, Thomas S, Ondo W, Rye D, Forbes A, Tluk S, Dhawan V, Bowron A, Williams AJ, Olanow CW. · Movement Disorders Unit, Kings College Hospital, University Hospital Lewisham, Guy's King's and St. Thomas' School of Medicine, London, United Kingdom. · Mov Disord. · Pubmed #16547944 No free full text.

Abstract: Nonmotor symptoms (NMS) of Parkinson's 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.

Stacy M, Bowron A, Guttman M, Hauser R, Hughes K, Larsen JP, LeWitt P, Oertel W, Quinn N, Sethi K, Stocchi F. · Duke University Medical Center, 932 Morreene Road, Durham, NC 27705, USA. · Mov Disord. · Pubmed #15719426 No free full text.

Abstract: This study compares the sensitivity of a Patient Questionnaire versus information gathered by clinicians at a routine clinic visit in recognizing symptoms of wearing-off in early Parkinson's disease (PD). This Patient Questionnaire, containing 32 items representing a wide spectrum of motor and nonmotor wearing-off symptoms, was administered to subjects attending two PD clinics. The Patient Questionnaire results were compared to the information gathered by the clinician from the Unified Parkinson's Disease Rating Scale (UPDRS) Part IV, Question 36 and from a specific Clinical Assessment Question regarding loss of medication efficacy, wearing-off, sleepiness, dyskinesias, psychiatric complications, morning akinesia, other dopaminergic side effects, or none of the above. Examiners were blinded to study hypothesis and survey contents. Three hundred consecutive subjects with PD of <5 years duration were evaluated; the mean subject age was 72 +/- 9.6 years and 60.2% were men. Subjects reporting wearing-off were significantly younger (69.9 vs. 74.7 years) and differed regarding duration of PD symptoms (3.7 vs. 3.1 years). Wearing-off was found in 181 subjects (62.6%) by one or more of the three measures. The most sensitive tool was the Patient Questionnaire, with 165 subjects (57.1%) indicating symptoms of wearing-off. Question 36 of the UPDRS was positive in 127 subjects (43.9%), and the Clinical Assessment Question identified 85 subjects (29.4%) as experiencing wearing-off. All of these results were found to differ significantly. The mean number of wearing-off symptoms reported by the 165 subjects indicating wearing-off on the clinical survey was 6.25, with tremor being the most common motor feature and tiredness the most common nonmotor feature.

Chong RK, Barbas J, Garrison K, Herolz A, Teheng R, Sethi K. · Department of Physical Therapy, Medical College of Georgia, CH-100, Augusta, GA, USA. · Int J Clin Pract. · Pubmed #11501233 No free full text.

Abstract: Patients with Parkinson's disease (PD) walk slowly, in part to compensate for their balance control deficit. We tested the effect of balance support to determine if walking performance in PD patients would improve. The sample consisted of unmedicated older adults with idiopathic Parkinson's disease who had poor balance control but no stooped posture, arthritis or muscle weakness. There was no difference in walking speed between unsupported and supported walking. The speeds were between those reported for disease-free older adults and older adults with muscle weakness and a history of falling. PD patients' walking difficulties, even while using a balance aid, may be partly explained by their set-changing problems. They frequently hold the cane off the ground when walking, suggesting their set-changing difficulty may be severe enough that using it aggravates their walking difficulty. Treatment of walking difficulty in PD patients should consider interventions other than those dealing only with balance control.