Parkinson Disease: Kompoliti K

Chou KL, Evatt M, Hinson V, Kompoliti K. · Department of Clinical Neurosciences, Warren Alpert Medical School of Brown University, Providence, Rhode Island, USA. · Mov Disord. · Pubmed #17659637 No free full text.

Abstract: A significant number of patients with Parkinson's disease (PD) experience sialorrhea. This problem can cause social embarrassment, and because saliva pools in the mouth, may lead to aspiration pneumonia. Sialorrhea in PD is thought to be caused by impaired or infrequent swallowing, rather than hypersecretion. Oral medications, botulinum toxin injections, surgical interventions, radiotherapy, speech therapy, and trials of devices may be used to treat sialorrhea in PD, but few controlled trials have been published. This article reviews current knowledge regarding the frequency, etiology, assessment, and treatment of sialorrhea in PD.

Kompoliti K. · Department of Neurological Sciences, Section of Movement Disorders, Rush-Presbyterian-St. Luke's Medical Center, Rush University, Chicago, IL 60546, USA. · Front Biosci. · Pubmed #12700049 No free full text.

Abstract: Female sex hormones, and more specifically estrogen, can have biochemical and behavioral effects on the dopaminergic system. The effects of estrogen on the dopaminergic system can be classified as either neuroprotective or symptomatic. The neuroprotective effects refer to the ability of estrogen to prevent or modulate insults to the dopaminergic system and therefore to alter the natural history of disease processes affecting the dopaminergic circuitry in the brain. With regards to the symptomatic effects, support for both suppressive and enhancing effects has been documented in humans and laboratory animals. The pre-clinical literature for neuroprotective and symptomatic effects of estrogen on the mesostriatal dopaminergic system forms the basis for studies on the influence of estrogen on the prevalence, disease progression, clinical signs, and medication effects of Parkinson's disease and other movement disorders. Understanding the role of estrogen in modulating the dopaminergic system will allow clinicians to tailor therapies for women with Parkinson's disease and optimize therapies for menstrually related symptom fluctuations. Such clarifications may also guide recommendations on the use of postmenopausal hormonal replacement therapy in women with Parkinson's disease or those genetically at risk.

Kompoliti K. · Department of Neurological Sciences, Rush-Presbyterian-St Luke's Medical Center, Rush University, Chicago, Illinois, USA. · Clin Neuropharmacol. · Pubmed #10626091 No free full text.

Abstract: Female sex hormones, and more specifically estrogen, can have biochemical and behavioral effects on the dopaminergic system. The effects of estrogen on the dopaminergic system can be classified as either neuroprotective or symptomatic. The neuroprotective effects refer to the ability of estrogen to prevent or modulate insults to the dopaminergic system and therefore to alter the natural history of disease processes affecting the dopaminergic circuitry in the brain. With regard to the symptomatic effects, support for suppressive and enhancing effects has been documented in humans and laboratory animals. The preclinical literature for neuroprotective and symptomatic effects of estrogen on the mesostriatal dopaminergic system forms the basis for studies on the influence of estrogen on the prevalence, disease progression, clinical signs, and medication effects of movement disorders, including Parkinson's disease, chorea, dystonia, tics, and myoclonus. Understanding the role of estrogen in modulating the dopaminergic system will allow clinicians to tailor therapies for women with movement disorders and optimize therapies for menstrually related symptom fluctuations. Such clarifications may also guide recommendations on the use of postmenopausal hormonal replacement therapy in women with movement disorders or those genetically at risk.

Cubo E, Kompoliti K, Leurgans SE, Raman R. · Sanatorio del Rosario, Clinica de la Zarzuela, Department of Neurology, Madrid, Spain. · Clin Neuropharmacol. · Pubmed #15090934 No free full text.

Abstract: Because migraine has been associated with dopaminergic receptor hypersensitivity, the authors hypothesized that patients with Parkinson disease with current or prior migraine have better dopaminergic response and less motor disability than Parkinson disease patients without migraine. Twenty-eight patients with Parkinson disease were included and matched (10 patients with migraine and 18 patients without migraine). Patients with Parkinson disease and migraine showed greater motor improvement during the ON state than patients without migraine with the same medication exposure. These data support the hypothesis that migraine may be associated with dopaminergic hypersensitivity.

Shults CW, Oakes D, Kieburtz K, Beal MF, Haas R, Plumb S, Juncos JL, Nutt J, Shoulson I, Carter J, Kompoliti K, Perlmutter JS, Reich S, Stern M, Watts RL, Kurlan R, Molho E, Harrison M, Lew M, Anonymous00266. · Department of Neurosciences, Mail Code 0662, University of California-San Diego, 9500 Gilman Dr, La Jolla, CA 92093-0662, USA. · Arch Neurol. · Pubmed #12374491 links to  free full text

Abstract: BACKGROUND: Parkinson disease (PD) is a degenerative neurological disorder for which no treatment has been shown to slow the progression. OBJECTIVE: To determine whether a range of dosages of coenzyme Q10 is safe and well tolerated and could slow the functional decline in PD. DESIGN: Multicenter, randomized, parallel-group, placebo-controlled, double-blind, dosage-ranging trial. SETTING: Academic movement disorders clinics. PATIENTS: Eighty subjects with early PD who did not require treatment for their disability. INTERVENTIONS: Random assignment to placebo or coenzyme Q10 at dosages of 300, 600, or 1200 mg/d. MAIN OUTCOME MEASURE: The subjects underwent evaluation with the Unified Parkinson Disease Rating Scale (UPDRS) at the screening, baseline, and 1-, 4-, 8-, 12-, and 16-month visits. They were followed up for 16 months or until disability requiring treatment with levodopa had developed. The primary response variable was the change in the total score on the UPDRS from baseline to the last visit. RESULTS: The adjusted mean total UPDRS changes were +11.99 for the placebo group, +8.81 for the 300-mg/d group, +10.82 for the 600-mg/d group, and +6.69 for the 1200-mg/d group. The P value for the primary analysis, a test for a linear trend between the dosage and the mean change in the total UPDRS score, was.09, which met our prespecified criteria for a positive trend for the trial. A prespecified, secondary analysis was the comparison of each treatment group with the placebo group, and the difference between the 1200-mg/d and placebo groups was significant (P =.04). CONCLUSIONS: Coenzyme Q10 was safe and well tolerated at dosages of up to 1200 mg/d. Less disability developed in subjects assigned to coenzyme Q10 than in those assigned to placebo, and the benefit was greatest in subjects receiving the highest dosage. Coenzyme Q10 appears to slow the progressive deterioration of function in PD, but these results need to be confirmed in a larger study.

Kompoliti K, Adler CH, Raman R, Pincus JH, Leibowitz MT, Ferry JJ, Blasucci L, Caviness JN, Leurgans S, Chase WM, Yones LC, Tan E, Carvey P, Goetz CG. · Department of Neurological Science, Rush-Presbyterian-St Luke's Medical Center, Chicago, IL 60612, USA. · Neurology. · Pubmed #12011296 No free full text.

Abstract: The authors studied the pharmacokinetics of levodopa (LD) with and without pramipexole (PPX) in men and postmenopausal women with PD. Patients on stable dose of carbidopa/LD were randomized to receive escalating doses of placebo or PPX over 7 weeks. LD and PPX pharmacokinetics were performed after a single test dose 25/100 of carbidopa/LD, before initiation of PPX or placebo, at 1.5 mg/d and 4.5 mg/d of PPX or placebo. Compared to men, women had greater LD bioavailability. PPX did not alter LD bioavailability, and PPX pharmacokinetics were equivalent in men and women.

Kompoliti K, Goetz CG, Leurgans S, Morrissey M, Siegel IM. · Department of Neurology, Rush-Presbyterian-St. Luke's Medical Center, Chicago, Illinois 60612, USA. · Mov Disord. · Pubmed #10752582 No free full text.

Abstract: OBJECTIVE: To measure "on" freezing during unassisted walking (UW) and test if two devices, a modified inverted stick (MIS) and a visual laser beam stick (LBS) improved walking speed and number of "on" freezing episodes in patients with Parkinson's disease (PD). BACKGROUND: Multiple visual cues can overcome "off' freezing episodes and can be useful in improving gait function in parkinsonian patients. These devices have not been specifically tested in "on" freezing, which is unresponsive to pharmacologic manipulations. METHODS: Patients with PD, motor fluctuations and freezing while "on," attempted walking on a 60-ft track with each of three walking conditions in a randomized order: UW, MIS, and LBS. Total time to complete a trial, number of freezes, and the ratio of walking time to the number of freezes were compared using Friedman's test. RESULTS: Twenty-eight patients with PD, mean age 67.81 years (standard deviation [SD] 7.54), mean disease duration 13.04 years (SD 7.49), and mean motor Unified Parkinson's Disease Rating Scale score "on" 32.59 (SD 10.93), participated in the study. There was a statistically significant correlation of time needed to complete a trial and number of freezes for all three conditions (Spearman correlations: UW 0.973, LBS 0.0.930, and MIS 0.842). The median number of freezes, median time to walk in each condition, and median walking time per freeze were not significantly different in pairwise comparisons of the three conditions (Friedman's test). Of the 28 subjects, six showed improvement with the MIS and six with the LBS in at least one outcome measure. CONCLUSION: Assisting devices, specifically based on visual cues, are not consistently beneficial in overcoming "on" freezing in most patients with PD. Because this is an otherwise untreatable clinical problem and because occasional subjects do respond, cautious trials of such devices under the supervision of a health professional should be conducted to identify those patients who might benefit from their long-term use.

Kompoliti K, Wang QE, Goetz CG, Leurgans S, Raman R. · Department of Neurological Sciences, Rush-Presbyterian-St. Luke's Medical Center, Rush University, Chicago, IL, USA. · Neurology. · Pubmed #10668714 No free full text.

Abstract: OBJECTIVE: To determine the effect of central dopaminergic stimulation with apomorphine on speech in PD. BACKGROUND: Most patients with PD have a speech disorder. Of those, 89% have involvement of laryngeal function, and 45% have additional articulatory dysfunction. The effect of dopaminergic medications on these two dimensions of speech impairment in PD has not been selectively studied. METHODS: In a randomized, double-blind, placebo-controlled crossover design, patients with PD and speech impairment, Hoehn and Yahr stages 2 to 4 "off," and without severe dyskinesias were given placebo or apomorphine injections 0.05 mg/kg subcutaneously during two consecutive outpatient visits. They were pretreated with domperidone for 48 hours and were tested off their parkinsonian medications for 12 hours. Laryngeal function was assessed by maximum sustained vowel phonations and comfortable vowel phonations. Articulatory function was evaluated by speech intelligibility score, speaking rate, and efficiency ratio. RESULTS: Ten patients, mean age 73.4 years (SD = 6.6), disease duration 8.7 years (SD = 6.3), were tested. The baseline motor score on the Unified Parkinson's Disease Rating Scale (UPDRSm) and all experimental speech variables were equivalent on both placebo and apomorphine days. At a dose of apomorphine that provoked improvement in UPDRSm (p = 0.0078), no index of either laryngeal or articulatory function improved significantly after apomorphine administration. CONCLUSION: Laryngeal and articulatory speech components are not under prominent dopaminergic control in PD. Treatment regimens should focus on nondopaminergic pharmacology and other therapies.

Kompoliti K, Chu Y, Shannon KM, Kordower JH. · Department of Neurological Sciences, Rush University Medical Center, Chicago, Illinois 60612, USA. · Mov Disord. · Pubmed #17534949 No free full text.

Abstract: To date, there is no clinicopathological correlation of adrenal medullary transplant cases in patients with survival beyond a few years. Postmortem examination of a brain from a patient with Parkinson's disease (PD), 16 years after autologous adrenal medullary transplant, was performed using tyrosine hydroxylase (TH) and chromogranin A. The patient experienced a four-year initial improvement in motor function followed by resumption of the progressive nature of her disease that continued until her death. She expired 16 years following grafting. At autopsy, TH stain of the brain revealed severe loss of TH-immunoreactivity in the substantia nigra and Lewy bodies, confirming the diagnosis of PD. The transplant site was identified by the presence of scarring and there was complete absence of any TH staining cells at the site of the transplant. There were few surviving cells staining with chromogranin A. The absence of TH-staining cells in the transplant 16 years after surgery provides further evidence that adrenal medullary transplants do not survive in the long term.

Chu Y, Le W, Kompoliti K, Jankovic J, Mufson EJ, Kordower JH. · Department of Neurological Science, Rush University Medical Center, Chicago, Illinois 60612, USA. · J Comp Neurol. · Pubmed #16320253 links to  free full text

Abstract: In mammals, the transcription factor Nurr1 is expressed early in development and continues to be detectable throughout the organism's lifetime. Nurr1 is involved in the establishment and maintenance of the dopaminergic phenotype within specific central nervous system neuronal subpopulations including the nigrostriatal dopamine system. This protein is reduced over the course of normal aging, which is a major risk factor for Parkinson's disease (PD). However, whether Nurr1 expression is affected by PD has not been documented. The present study examined the role of Nurr1 in the maintenance of the dopaminergic phenotype within neurons in substantia nigra in PD compared with patients with diagnoses of progressive supranuclear palsy (PSP) or Alzheimer's disease (AD) or age-matched-matched controls. In PD, the optical density (OD) of Nurr1 immunofluorescence was significantly decreased in nigral neurons containing alpha-synuclein-immunoreactive inclusions. Similarly, the OD of Nurr1 immunofluorescence intensity in the nigra of AD cases was decreased in neurons with neurofibrillary tangles (NFTs). In contrast to PD and AD, the OD of Nurr1 immunofluorescence intensity was severely decreased in the neurons with or without NFTs in PSP cases. Decline of Nurr1-ir neuronal number and OD was observed within substantia nigra (SN) neurons in PD but not within hippocampal neurons. The decline in Nurr1-ir expression was correlated with loss of tyrosine hydroxylase immunofluorescence across the four groups. These data demonstrate that Nurr1 deficiency in dopaminergic neurons is associated with the intracellular pathology in both synucleinopathies and tauopathies.

Diederich NJ, Goebel HH, Dooms G, Bumb A, Huber F, Kompoliti K, Meinck HM. · Department of Neuroscience, Centre Hospitalier de Luxembourg, Luxembourg, Luxembourg. · Mov Disord. · Pubmed #16211611 No free full text.

Abstract: Camptocormia (CC) or pronounced forward flexion of the trunk is a common symptom of Parkinson's disease. We describe 2 patients with probable, respectively possible multiple-system atrophy and CC. Magnetic resonance imaging of the erector trunci showed focal patchy hyperintensities with gadolinium enhancement and muscle biopsy was indicative of variably pronounced focal myositis. CC was progressive and the major handicap for both patients after 1 and 1.5 years of follow-up, respectively. The therapeutic response was poor. Similarities with the dropped-head syndrome suggest that the muscle pathology may be either the primary cause of CC, a focal reaction to the CC posture, or a coincident syndrome of old age.

Cubo E, Rojo A, Ramos S, Quintana S, Gonzalez M, Kompoliti K, Aguilar M. · Neurology Department, Hospital Mutua de Terrassa, Terrassa (Barcelona), Spain. · Eur J Neurol. · Pubmed #12453073 No free full text.

Abstract: OBJECTIVE: To define the factors correlated with quality of life (QoL) in patients with idiopathic Parkinson's disease (PD). BACKGROUND: PD has a substantial impact on QoL. Although several clinical factors have been associated with QoL in PD, the influence of patient's education still remains controversial. METHODOLOGY: A consecutive series of patients with PD were examined using the unified Parkinson's Disease Rating Scale (UPDRS part I, II, III), Schwab and England (SE), and Hoehn and Yahr stage (H&Y). QoL was rated with the PDQ-39, cognition with the Mini-Mental State examination (MMSE), and the presence of depressive symptoms with the geriatric depression scale (GDS). Patient's characteristics, estimated cumulative levodopa dose (CLD), UPDRS, H&Y, MMSE and GDS were correlated with the PDQ-39 using univariate and multiple regression analysis. RESULTS: A total of one hundred 58 patients (68 men, 90 women) with a mean age of 65.6 +/- 9.3 years, PD duration of 8.1 +/- 10.6 years, and education of 6.6 +/- 3.9 years were included. The mean PDQ-39 was 48.8 +/- 27.8, mean MMSE was 25.7 +/- 4, and mean GDS was 11.7 +/- 6.8. Using stepwise multiple regression analysis, the most important predictive factors were depression, UPDRS part I, UPDRS part II, and educational background, which accounted for a 61% of the variability of the PDQ-39 scores. CONCLUSIONS: In our PD sample, educational, behavioural, and psychological factors influenced life satisfaction more than physical ones.

Chu Y, Kompoliti K, Cochran EJ, Mufson EJ, Kordower JH. · Department of Neurological Sciences, Rush Presbyterian-St. Luke's Medical Center, Chicago, Illinois 60612, USA. · J Comp Neurol. · Pubmed #12209851 No free full text.

Abstract: Nuclear receptor-related factor 1 (Nurr1), a member of the nuclear receptor superfamily, is associated with the induction of dopaminergic (DA) phenotypes in developing and mature midbrain neurons. It is well established that dopaminergic nigrostriatal function decreases with age. Whether age-related deficits in DA phenotypic markers are associated with alterations in Nurr1 expression is unknown. The present study found that virtually all of tyrosine hydroxylase-immunoreactive (TH-ir) neurons within the young adult human substantia nigra were Nurr1-immunoreactive (Nurr1-ir) positive. Stereologic counts revealed a significant reduction in the number of Nurr1-ir nigral neurons in middle-aged (23.13%) and aged (46.33%) individuals relative to young subjects. The loss of Nurr1-ir neurons was associated with a similar decline in TH-ir neuron number. In this regard, TH-ir neuronal number was decreased in middle-aged (11.10%) and in aged (45.97%) subjects, and this loss of TH-ir neurons was highly correlated (r = 0.92) with the loss of Nurr1-ir neurons. In contrast, the number of melanin-containing nigral neuron number was generally stable across age groups, indicating that changes in Nurr1 and TH reflect phenotypic age-related changes and not frank neuronal degeneration. In support of this concept, confocal microscopic analyses of Nurr1-ir and TH-ir fluorescence intensity revealed parallel decreases in Nurr1- and TH-immunofluorescence as a function of age. These data demonstrate that age-related decline of DA phenotypic markers is associated with down-regulation of Nurr1 expression in the SN.

Kompoliti K, Comella CL, Jaglin JA, Leurgans S, Raman R, Goetz CG. · Department of Neurological Sciences, Rush-Presbyterian-St Luke's Medical Center, Rush University, Chicago, IL, USA. · Neurology. · Pubmed #11094119 No free full text.

Abstract: Questionnaire studies have found that parkinsonism worsens in women during the premenstrual period, when estrogen and progesterone levels are presumably at their nadir. To assess this patient-based observation and correlate motor signs with hormonal levels, the authors prospectively studied 10 menstruating women with PD in their "off" state, on 5 successive weeks. Although PD severity fluctuated during the study period, there was no significant correlation between the objective or subjective measures of parkinsonism and estrogen and progesterone levels.

Cubo E, Stebbins GT, Golbe LI, Nieves A, Leurgans S, Goetz CG, Kompoliti K. · Department of Neurological Sciences, Rush-Presbyterian-St. Luke's Medical Center, Chicago, Illinois 60612, USA. · Mov Disord. · Pubmed #10752576 No free full text.

Abstract: An important criterion in scale validation is the demonstration of a stable factor structure. The Unified Parkinson's Disease Rating Scale (UPDRS) is widely used to assess Parkinson's disease (PD). The reliability and applicability of the motor subscale of the UPDRS (UPDRSm) when applied to patients diagnosed with progressive supranuclear palsy (PSP) is unknown. In a sample of 175 patients with PSP, factor analysis revealed five clinically distinct factors: two independent bradykinesia factors (axial/gait and extremities), one rigidity factor, and two independent tremor factors (rest and action). Two items (posture and rest head tremor) did not reach criteria for factor loadings. There was a high degree of internal consistency. These results suggest that UPDRSm is a reliable and applicable scale for assessing most aspects of PSP function as well as severity measures of five clinical disability domains.