Showing papers by "Kapil D. Sethi published in 2006"
King's College1, Carlos III Health Institute2, University College London3, Georgia Regents University4, King's College London5, University of North Carolina at Chapel Hill6, University of Naples Federico II7, Southern General Hospital8, Tel Aviv University9, Royal College of Nursing10, Baylor College of Medicine11, Emory University12, University of Cambridge13, North Tyneside General Hospital14, St Thomas' Hospital15, Icahn School of Medicine at Mount Sinai16
TL;DR: An international pilot study assessing feasibility, validity, and acceptability of a nonmotor questionnaire (NMSQuest) found NMS were highly significantly more prevalent across all disease stages and the number of symptoms correlated significantly with advancing disease and duration of disease.
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.
874 citations
Baylor College of Medicine1, Mayo Clinic2, Indiana University – Purdue University Indianapolis3, Rush University Medical Center4, North Shore-LIJ Health System5, Case Western Reserve University6, Georgia Regents University7, University of Miami8, St. Joseph's Hospital and Medical Center9, Harvard University10
TL;DR: The high antigenicity of BTX-B limits its long-term efficacy in cervical dystonia and is correlated with the clinical response with the presence of blocking antibodies using a novel mouse protection assay.
Abstract: In this multicenter study of 100 patients with cervical dystonia, we examined the immunogenicity of botulinum toxin type B (BTX-B) and correlated the clinical response with the presence of blocking antibodies (Abs) using a novel mouse protection assay. One-third of the patients who were negative for BTX-B Abs at baseline became positive for BTX-B Abs at last visit. Thus, the high antigenicity of BTX-B limits its long-term efficacy.
81 citations
TL;DR: Based on this limited survey of treating physicians in the USA, btxA appears to be relatively safe for both expectant mother and fetus, and it is recommended that physicians and patients carefully consider the risks and benefits before using this drug in pregnant women.
Abstract: Botulinum toxin A (btxA) is widely used for cosmetic purposes, headaches, dystonia, spasticity, pain and other on and off label uses. Despite the widespread use of btxA in women of childbearing potential, there are few data on the effects of this drug on pregnant women and the fetus. The goal of this study was to survey physicians who use btxA, to determine their experience with pregnant women. We surveyed 900 physicians who used commercially available btxA. The questionnaire asked treating physicians if they had knowingly or unknowingly injected pregnant women and what was the outcome of each pregnancy. In total, 396 physicians (44%) returned questionnaires, of whom only 12 physicians reported injecting pregnant women with btxA. Sixteen pregnant women were injected, mostly in the first trimester, and only one patient, who had prior spontaneous abortions, suffered a miscarriage. Another woman had a therapeutic abortion. All other pregnancies went to term and there were no fetal malformations. Based on this limited survey of treating physicians in the USA, btxA appears to be relatively safe for both expectant mother and fetus. We need further data, however, and we would recommend that physicians and patients carefully consider the risks and benefits before using btxA in pregnant women.
79 citations
TL;DR: 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.
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.
71 citations
TL;DR: The history of postural instability first described as a feature of PD by Romberg in 1853 is traced and the name “Fahn pull test” is proposed for the maneuver based on his significant contribution to its development.
Abstract: The pull test (PT) is used as a measure of postural instability in Parkinson's disease (PD) and other movement disorders. In 1987, it was incorporated into the Unified Parkinson's Disease Rating Scale (UPDRS), a scale used to measure the severity and treatment response in PD both in research studies and in clinical practice. However, the origins of the observation of postural instability in movement disorders and the attempt to quantify it are much older. Here, we trace the history of postural instability first described as a feature of PD by Romberg in 1853. Attempts to evaluate postural instability began with the first measurement by Charcot in the 1880s by pulling the clothes of patients and progressed to the push on the sternum by Hoehn and Yahr in the 1960s. Eventually, this evolved into the formal PT proposed by Fahn in the 1980s. Despite the widespread use of the PT as part of the UPDRS, variability exists in its execution. Recommendations have been made for training of examiners in clinical trials to improve its accuracy in assessing postural instability. We agree with improving PT technique for clinical trials and advocate for its routine use in clinical practice when diagnosing and treating movement disorders. Further, we propose the name "Fahn pull test" for the maneuver based on his significant contribution to its development.
66 citations
Johns Hopkins University1, University of Rochester2, Medical College of Wisconsin3, University of Pennsylvania4, Columbia University5, University of Southern California6, University of South Florida7, Rutgers University8, Indiana University9, North Shore-LIJ Health System10, Baylor College of Medicine11, Virginia Commonwealth University12, University of Alabama at Birmingham13, University of Toronto14, Ohio State University15, University of Kansas16, Albany Medical College17, University of Miami18, University of Saskatchewan19, St. Joseph's Hospital and Medical Center20, Creighton University21, University of Minnesota22, Rush University Medical Center23, Yale University24, University of California, San Francisco25, University of Chicago26, Georgia Regents University27, University of Alberta28, Mayo Clinic29, Boston University30, Oregon Health & Science University31, University of Connecticut32
TL;DR: Rasagiline improved QOL compared with placebo, and this QOL improvement appears to be accounted for primarily by the symptomatic benefit of rasagILine.
Abstract: The objective of this study was to determine the effects of rasagiline as monotherapy on quality of life (QOL) in patients with early Parkinson's disease (PD). Rasagiline, a potent, second-generation, irreversible, selective monoamine oxidase B inhibitor improves PD symptoms in patients with early PD. Patients with early untreated PD were randomly assigned to once-daily rasagiline 1 mg/day, rasagiline 2 mg/day, or placebo in a 6-month, double-blind trial (n=404). At the end of 6 months, patients entered the preplanned, active-treatment phase in which those receiving 1 mg/day and 2 mg/day of rasagiline continued on their previously assigned dosages and those receiving placebo switched to rasagiline 2 mg/day, while maintaining blinding to treatment assignments. QOL was measured with the Parkinson's Disease Quality of Life questionnaire (PDQUALIF) at 0, 14, 26, and 52 weeks after randomization. Analysis of the change in PDQUALIF scores from baseline to 6 months showed adjusted treatment effects (with 95% confidence interval) favoring rasagiline over placebo of -2.91 units (-5.19, -0.64, P=0.01) for the 1 mg/day group and -2.74 units (-5.02, -0.45, P=0.02) for the 2 mg/day. Subscore analysis attributed most of this benefit to the self-image/sexuality domain. At 12 months (n=266), with all groups receiving rasagiline for at least 6 months, no significant differences in PDQUALIF scores were seen between groups. Rasagiline improved QOL compared with placebo. This QOL improvement appears to be accounted for primarily by the symptomatic benefit of rasagiline.
61 citations
Southern Illinois University Carbondale1, University of Alabama at Birmingham2, Georgia Regents University3, University of Kansas4, Rush University Medical Center5, Columbia University6, National Institutes of Health7, Baylor College of Medicine8, Emory University9, University of Pennsylvania10, Houston Methodist Hospital11
TL;DR: The conference attendees concluded that a collaborative network of research centers and an international committee for developing a standard protocol for the diagnosis and quantification of ET are of immediate and overriding importance.
Abstract: Seventy researchers met in Washington, DC, on 20-21 October 2005 to identify and discuss the most pressing research issues in essential tremor (ET). The conference attendees concluded that the following six objectives are of immediate and overriding importance: (1) a collaborative network of research centers; (2) an international committee for developing a standard protocol for the diagnosis and quantification of ET; (3) the identification of one or more genes for ET; (4) a centralized repository of DNA and, ideally, immortalized cell lines from well-characterized ET families and healthy controls; (5) a reliable and efficient repository of optimally prepared and categorized brain samples for hypothesis-driven neuropathological examinations in well-characterized ET patients; and (6) animal models of ET for screening promising drugs. The conference attendees hope that this statement from the United States will engender international collaboration in finding a cure for ET.
45 citations
TL;DR: This work reports a pilot association study of the beta-glucocerebrosidase N370S allele and Parkinson’s disease in subjects of Jewish ethnicity and analysis of 304 mutant alleles in patients with type 1 and type 3 Gaucher disease.
Abstract: 1. Clark LN, Nicolai A, Afridi S, et al. Pilot association study of the beta-glucocerebrosidase N370S allele and Parkinson’s disease in subjects of Jewish ethnicity. Mov Disord 2005;20:100–103. 2. Sato C, Morgan A, Lang AE, et al. Analysis of the glucocerebrosidase gene in Parkinson’s disease. Mov Disord 2005;20:367–370. 3. Neudorfer O, Giladi N, Elstein D, et al. Occurrence of Parkinson’s syndrome in type I Gaucher disease. Q J Med 1996;89:691–694. 4. Tayebi N, Walker J, Stubblefield B, et al. Gaucher disease with parkinsonian manifestations: does glucocerebrosidase deficiency contribute to a vulnerability to parkinsonism? Mol Genet Metab 2003;79:104–109. 5. Wong K, Sidransky E, Verma A, et al. Neuropathology provides clues to the pathophysiology of Gaucher disease. Mol Genet Metab 2004;82:192–207. 6. Goker-Alpan O, Schiffmann R, LaMarca ME, Nussbaum RL, McInerney-Leo A, Sidransky E. Parkinsonism among Gaucher disease carriers. J Med Genet 2004;41:937–940. 7. Lwin A, Orvisky E, Goker-Alpan O, LaMarca ME, Sidransky E. Glucocerebrosidase mutations in subjects with parkinsonism. Mol Genet Metab 2004;81:70–73. 8. Eblan MJ, Walker JM, Sidransky E. The glucocerebrosidase gene and Parkinson’s disease in Ashkenazi Jews. N Engl J Med 2005; 352:728–731; author reply 728–731. 9. Aharon-Peretz J, Rosenbaum H, Gershoni-Baruch R. Mutations in the glucocerebrosidase gene and Parkinson’s disease in Ashkenazi Jews. N Engl J Med 2004;351:1972–1977. 10. Koprivica V, Stone DL, Park JK, et al. Analysis and classification of 304 mutant alleles in patients with type 1 and type 3 Gaucher disease. Am J Hum Genet 2000;66:1777–1786. 11. Dvir H, Harel M, McCarthy AA, et al. X-ray structure of human acid-beta-glucosidase, the defective enzyme in Gaucher disease. EMBO Rep 2003;4:704–709.
36 citations
Indiana University1, Cincinnati Children's Hospital Medical Center2, University of Rochester3, United States Department of Veterans Affairs4, University of California, San Diego5, University of Cincinnati6, Columbia University7, University of Kansas8, Eli Lilly and Company9, Albany Medical College10, Baylor College of Medicine11, Harvard University12, Yeshiva University13, Brown University14, Cleveland Clinic15, Creighton University16, LSU Health Sciences Center New Orleans17, McGill University18, University Medical Center New Orleans19, Johns Hopkins University20, University of Western Ontario21, Mayo Clinic22, Georgia Regents University23, Medical College of Wisconsin24, Ohio University25, Icahn School of Medicine at Mount Sinai26, North Shore-LIJ Health System27, Northwestern University28
TL;DR: Although the G2019S mutation remains the most common mutation identified in familial PD patients, other mutations in LRRK2 are infrequent and only 1 of the 12 newly screened mutations, R1441C, was detected in a single family in the patient cohort.
Abstract: A total of 956 individuals with Parkinson's disease (PD) from 430 multiplex PD pedigrees were screened for 12 previously reported, pathogenic LRRK2 mutations: R793M, L1114L, I1371V, R1441C, R1441G, R1441H, Y1699C, M1869T, I2012T, I2020T, G2385R, and IVS31 +3G > A. Previous screening identified the LRRK2 G2019S mutation in 5% of our families. Only 1 of the 12 newly screened mutations, R1441C, was detected in a single family in our patient cohort. These results indicate that, although the G2019S mutation remains the most common mutation identified in familial PD patients, other mutations in LRRK2 are infrequent.
30 citations
TL;DR: This review discusses emerging drugs in the management of the motor and nonmotor symptoms of PD and drugs under study as disease-slowing/neuroprotective agents.
Abstract: Parkinson's disease (PD) afflicts millions of people worldwide. There are numerous drugs available for PD; however, levodopa remains the gold standard of pharmacotherapy to which all other therapies are compared. Levodopa is quite effective for many motor symptoms (bradykinesia, tremor, rigidity) of PD; however, non-levodopa-responsive motor symptoms (postural instability) and nonmotor symptoms are frequently the most troublesome in middle and later stages of disease. Although motor symptoms remain an important focus for emerging drugs, current research is largely geared to identify and develop disease-slowing therapies. Another important area of focus has become treatment of the nonmotor symptoms of PD (especially depression and dementia). This review discusses emerging drugs in the management of the motor and nonmotor symptoms of PD and drugs under study as disease-slowing/neuroprotective agents.
22 citations
TL;DR: This report presents two patients who developed hiccups associated with dopamine agonist pharmacotherapy in Parkinson disease (PD) and explains why dopamine blocking agents (DBA) can be effective.
Abstract: Hiccups in adults are frequently due to gastric distention or alcohol consumption and are usually self-limited.1 In some instances, medications such as corticosteroids and benzodiazepines are implicated and discontinuing these agents typically results in resolution of the hiccups.2 In cases where hiccups become prolonged or intractable, dopamine blocking agents (DBA) can be effective.1 While dopaminergic therapies are implicated in the development of hiccups in pharmacovigilance surveys,3 we could not find a previous report of hiccups associated with dopamine agonists in the English language literature (PubMed). In this report we present two patients who developed hiccups associated with dopamine agonist pharmacotherapy in Parkinson disease (PD).
A 74-year-old man noted gradually progressive slowing of movements, left hand tremor, decreased voice volume, and shuffling gait. He was diagnosed with PD at age 76, initiated on carbidopa/levodopa, and improved. Pramipexole was added (by another physician) at a dose of 0.125 mg daily …
TL;DR: Rotigotine is a lipid-soluble, non-ergot, D3, D2, D1 dopamine receptor agonist that has demonstrated efficacy as an alternative therapeutic option in both early and advanced Parkinson’s disease and is uniquely formulated as a transdermal patch delivery system allowing for continuous, once-daily administration and better patient compliance.
Abstract: Dopaminergic therapies, including levodopa and dopamine agonists, are the mainstays of therapy in Parkinson's disease. With the exception of the injectable short-acting dopamine agonist apomorphine, there is no other widely available non-oral dopaminergic therapy. Rotigotine is a lipid-soluble, non-ergot, D3, D2, D1 dopamine receptor agonist that has demonstrated efficacy as an alternative therapeutic option in both early and advanced Parkinson's disease. More importantly, it is uniquely formulated as a transdermal patch delivery system allowing for continuous, once-daily administration and better patient compliance. Preclinical and clinical trials have shown rotigotine to be a well-tolerated and effective treatment for early-stage Parkinson's disease. Rotigotine has also shown promise as adjunctive therapy with levodopa for the treatment of advanced Parkinson's disease.
14 Mar 2006
TL;DR: Ergotism results from generalized vasoconstriction of small and large blood vessels and can lead to cyanosis and gangrene of affected limbs if not recognized.
Abstract: Ergotism results from generalized vasoconstriction of small and large blood vessels and can lead to cyanosis and gangrene of affected limbs if not recognized. Ergotism occurs most commonly in the treatment of migraine with ergotamines today; however, ergot-derived drugs are also used in the treatment of restless legs syndrome and …
01 Jan 2006