Symptoms, Management, and Risks: Parkinson's Disease
Symptoms, Management, and Risks: Parkinson's Disease
What is the latest research on symptoms, management, and risks for Parkinson's disease? Find out in this collection of recent MEDLINE abstracts compiled by the editors at Medscape Neurology & Neurosurgery.
Muller T, Voss B, Hellwig K, et al
CNS Drugs. 2004;18: 105-111
Objective: In some countries, such as Germany, there has been a move towards the treatment of patients with Parkinson's disease in specialised inpatient units. However, data on patient outcome and the daily costs of antiparkinsonian drugs in these settings are rare. This study was conducted to determine the effect of an inpatient setting (a specialised Parkinson's disease clinic) on drug therapy costs and patient symptoms.
Patients and Methods: This study involved 63 consecutively referred inpatients of a Parkinson's disease clinic. On entry to the clinic, the patients' antiparkinsonian drug regimen was titrated in order to improve their motor function. The daily costs of drug therapy per patient (in 2002 values) were calculated, and the severity of Parkinson's disease symptoms scored via scores on the Unified Parkinson's Disease Rating Scale (UPDRS) and standardised instrumental procedures (peg insertion and tapping), both initially and at the end of the patients' stay in the clinic. The variables between the two evaluation timepoints were compared.
Results: The titration of antiparkinsonian drugs was associated with a significant decrease in the symptoms of Parkinson's disease at discharge from the clinic compared with admission (as measured by UPDRS total and subscale scores [all p < 0.001], and, to a lesser extent, by peg insertion and tapping [both p < 0.05]). A significant increase in daily drug costs (an increase of euro14.11 per patient for all drugs and euro12.36 per patient for antiparkinsonian drugs [both p <0.001]) was also observed.
Conclusion: The results demonstrate that the symptoms experienced by patients with Parkinson's disease improve after performance of antiparkinsonian drug titration within the setting of a specialised Parkinson's disease clinic. The effect on symptoms was seen most clearly with the UPDRS, although both peg insertion and tapping reflected this improvement to a certain extent. Drug titration resulted in, on average, a doubling of daily drug costs. Future trials are needed to investigate the long-term effects of such a hospital stay on indirect costs associated with treating Parkinson's disease, and on caregiver burden, and also to compare the efficacy of a Parkinson's disease clinic with an outpatient setting.
Johnson AM, Almeida QJ, Stough C, et al
Neuropsychologia. 2004;42:577-583
Inspection time (IT) is a simple information processing paradigm dependent on a participant's ability to identify physical properties of a stimulus presented for a specified time interval. In contrast with reaction time (RT) studies, the dependent variable of interest in IT is not related to the motoric speed with which the individual is able to respond, but rather the minimum presentation time necessary for participants to reliably identify physical properties of the stimulus. It is well documented that individuals with Parkinson's disease (PD) experience significant impairment on tests of simple RT, but it is unclear whether such deficits can be interpreted as 'pure' slowness of information processing, or a delay in the selection and output of a motor response. In the first experiment described here, a sample of 'optimally medicated' PD patients was compared with an age-matched control group, on an IT task. Results of this experiment suggested that individuals with PD required significantly longer stimulus presentation times than healthy participants. The second experiment compared a sample of PD patients (tested both "ON" and "OFF" their typical dopaminergic medications), with an age-matched control group, on the same test of IT. Results again indicated a significant IT deficit in participants with PD, and suggested that these deficits do not significantly resolve with levodopa treatment. Overall, the results of these two experiments suggest that information processing deficits associated with PD are distinct from motor impairment. These findings are further discussed in terms of existing neurochemical models of information processing ability.
Ondo WG, Hunter C, Moore W
Neurology. 2004;62:37-40
Background: Injections of botulinum toxin A are an effective treatment for sialorrhea in Parkinson's disease (PD). Based on the relatively high rates of dry mouth seen with botulinum toxin B, there is reason to suspect that it may also improve sialorrhea.
Objective: To determine whether botulinum toxin B (Myobloc; Elan Pharmaceuticals, New York, NY) is a safe and effective treatment for sialorrhea in patients with PD.
Methods: Demographics, PD treatments, head posture, the Unified Parkinson's Disease Rating Scale (UPDRS), two questionnaires regarding drooling, Visual Analogue Scale, global impressions, salivary gland imaging, and a dysphagia questionnaire were assessed in 16 PD subjects with problematic sialorrhea. Patients were then randomized to receive either botulinum toxin B (1,000 units into each parotid gland and 250 units into each submandibular gland) or a pH-matched placebo, using only anatomic landmarks. Patients returned 1 month later to undergo an identical assessment.
Results: Compared with placebo, those randomized to drug reported improvement on the Visual Analogue Scale (p < 0.001), global impressions of change (p < 0.005), Drooling Rating Scale (p < 0.05), and Drooling Severity and Frequency Scale (p < 0.001). There was no change in UPDRS, head posture, or Dysphagia Scale. Adverse events were mild and included dry mouth (three patients), worsened gait (two), diarrhea (one), and neck pain (one) in the botulinum toxin B group.
Conclusion: Anatomically guided injections of botulinum toxin B into the parotid and submandibular glands appear to effectively improve sialorrhea without compromising dysphagia in patients with PD.
Kemoun G, Defebvre L, Watelain E, et al
Rev Neurol. 2003;159:1028-1037
Falls are a dramatic consequence of the age-related gait disorders. There are few prospective studies on falls predictive of the biomechanical features of gait. According to the literature, there are similarities between the gait observed in older people and in parkinsonian subjects. The objective of this study was to apply multiparametric gait analysis to demonstrate changes of the neuromotor gait pattern connected with falls. This prospective study included two groups of 16 subjects aged more than 60 years, who had not fallen during the previous year. One group included 16 minimally disabled parkinsonian patients off drugs, and the other group 16 healthy people. Gait recordings were obtained with a three-dimensional optoelectronic movement analysis system coupled with 2 force platforms in all persons who were followed for 1 year to collect data on all new events, particularly falls. Data analysis concerned spatiotemporal stride and three-dimensional power peaks developed in each lower limb joint. Cluster analysis of the 32 persons was used to determine various infraclinic neuromotor gait patterns. A post hoc analysis of variance was then applied to identify discriminating parameters. Three groups of subjects were identified with 3 different neuromotor gait patterns, independently of the presence of Parkinson disease. There were no fallers in first group (n=18). The second group (n=8) had 20 p.cent fallers and the third group (n=4) 100 p.cent fallers. The groups differed by 4 spatiotemporal parameters and 3 joint power peaks in the sagittal plane. Functional capacity was good in the first group with no falls recorded. This group of subjects had characteristics reported in the literature corresponding to a category of persons who compensate well for the phenomena of aging. Functional capacity was intermediary in the second group (20 p. cent were fallers). The kinematic pattern appeared to be less successful, revealing a tendency for stiff posture. The third group (100 p. cent fallers) exhibited inferior functional capacity. In this group, the kinematic pattern appeared to be disrupted. The subjects were unable to adapt satisfactorily to situations other than by stereotypical neuromotor reactions. In conclusion this study demonstrated a close determinism between physiological neuromotor aging and Parkinson's disease. The prospective follow-up demonstrated that falls that occurred were related to changes in neuromotor gait patterns. Three phases of gait pattern were also identified from minimal to major risk of falls.
Thomas A, Iacono D, Luciano AL, et al
J Neurol Neurosurg Psychiatry. 2004;75:141-143
Background: Recent short-term studies suggested that amantadine (Ama) might ameliorate dyskinesia in patients with Parkinson's disease. A double-blind study programmed over 12 months was designed to assess the duration of the antidyskinetic effect of amantadine on levodopa induced dyskinesia.
Methods: 40 patients treated for 7.5 (2.2) years with levodopa (729.3 (199.4) mg/day) and dopaminoagonists, having peak dose or dyphasic dyskinesia with or without pain, were assessed with the Unified Parkinson's Disease Rating Scale subscale IV, Items 32-34, the Dyskinesia Rating Scale and Investigator Global Assessment. Twenty patients received amantadine chloridrate (100 mg) and 20 received a placebo. The Ama or placebo could be withdrawn when scores indicated worsening of dyskinesia, after agreement with the patient.
Results: After 15 days of amantadine treatment there was a reduction by 45% in the total dyskinesia scores. All patients in the placebo group were withdrawn in 1-3 months and all patients in the Ama group were withdrawn in 3-8 months (p = 0.01, p<0.001). Ama withdrawal induced a rebound with increase of dyskinesia by 10-20% in 11 patients.
Conclusion: 300 mg amantadine reduces dyskinesia in Parkinson's disease by approximately 45% but the benefit lasted less than eight months.
Gorell JM, Peterson EL, Rybicki BA, Johnson CC
J Neurol Sci. 2004;217:169-174
Objective: To determine the relative contribution of various risk factors to the development of Parkinson's disease (PD).
Methods: Ten variables that were independently associated with PD in a health system population-based case-control study of epidemiological risk factors for the disease were jointly assessed. Stepwise logistic regression, adjusted for sex, race and age was used to develop a multiple variate model that best predicted the presence of PD. The population attributable risk was estimated for each variable in the final model, as well as for all factors together.
Results: The 10 initial variables included >20 years occupational exposure to manganese or to copper, individually; >20 years joint occupational exposure to either lead and copper, copper and iron, or lead and iron; a positive family history of PD in first- or second-degree relatives; occupational exposure to insecticides or herbicides; occupational exposure to farming; and smoking. Logistic regression resulted in a final model that included >20 years joint occupational exposure to lead and copper (p=0.009; population attributable risk [PAR]=3.9%), occupational exposure to insecticides (p=0.002; PAR=8.1%), a positive family history of PD in first- and second-degree relatives (p=0.001; PAR=12.4%), and smoking ≤30 pack-years or not smoking (p=0.005; PAR=41.4%). All four variables combined had a PAR=54.1%.
Conclusions: Our final model of PD risk suggests that occupational, environmental lifestyle and, likely, genetic factors, individually and collectively, play a significant role in the etiology of the disease. Clearly, additional risk factors remain to be determined through future research.
What is the latest research on symptoms, management, and risks for Parkinson's disease? Find out in this collection of recent MEDLINE abstracts compiled by the editors at Medscape Neurology & Neurosurgery.
Muller T, Voss B, Hellwig K, et al
CNS Drugs. 2004;18: 105-111
Objective: In some countries, such as Germany, there has been a move towards the treatment of patients with Parkinson's disease in specialised inpatient units. However, data on patient outcome and the daily costs of antiparkinsonian drugs in these settings are rare. This study was conducted to determine the effect of an inpatient setting (a specialised Parkinson's disease clinic) on drug therapy costs and patient symptoms.
Patients and Methods: This study involved 63 consecutively referred inpatients of a Parkinson's disease clinic. On entry to the clinic, the patients' antiparkinsonian drug regimen was titrated in order to improve their motor function. The daily costs of drug therapy per patient (in 2002 values) were calculated, and the severity of Parkinson's disease symptoms scored via scores on the Unified Parkinson's Disease Rating Scale (UPDRS) and standardised instrumental procedures (peg insertion and tapping), both initially and at the end of the patients' stay in the clinic. The variables between the two evaluation timepoints were compared.
Results: The titration of antiparkinsonian drugs was associated with a significant decrease in the symptoms of Parkinson's disease at discharge from the clinic compared with admission (as measured by UPDRS total and subscale scores [all p < 0.001], and, to a lesser extent, by peg insertion and tapping [both p < 0.05]). A significant increase in daily drug costs (an increase of euro14.11 per patient for all drugs and euro12.36 per patient for antiparkinsonian drugs [both p <0.001]) was also observed.
Conclusion: The results demonstrate that the symptoms experienced by patients with Parkinson's disease improve after performance of antiparkinsonian drug titration within the setting of a specialised Parkinson's disease clinic. The effect on symptoms was seen most clearly with the UPDRS, although both peg insertion and tapping reflected this improvement to a certain extent. Drug titration resulted in, on average, a doubling of daily drug costs. Future trials are needed to investigate the long-term effects of such a hospital stay on indirect costs associated with treating Parkinson's disease, and on caregiver burden, and also to compare the efficacy of a Parkinson's disease clinic with an outpatient setting.
Johnson AM, Almeida QJ, Stough C, et al
Neuropsychologia. 2004;42:577-583
Inspection time (IT) is a simple information processing paradigm dependent on a participant's ability to identify physical properties of a stimulus presented for a specified time interval. In contrast with reaction time (RT) studies, the dependent variable of interest in IT is not related to the motoric speed with which the individual is able to respond, but rather the minimum presentation time necessary for participants to reliably identify physical properties of the stimulus. It is well documented that individuals with Parkinson's disease (PD) experience significant impairment on tests of simple RT, but it is unclear whether such deficits can be interpreted as 'pure' slowness of information processing, or a delay in the selection and output of a motor response. In the first experiment described here, a sample of 'optimally medicated' PD patients was compared with an age-matched control group, on an IT task. Results of this experiment suggested that individuals with PD required significantly longer stimulus presentation times than healthy participants. The second experiment compared a sample of PD patients (tested both "ON" and "OFF" their typical dopaminergic medications), with an age-matched control group, on the same test of IT. Results again indicated a significant IT deficit in participants with PD, and suggested that these deficits do not significantly resolve with levodopa treatment. Overall, the results of these two experiments suggest that information processing deficits associated with PD are distinct from motor impairment. These findings are further discussed in terms of existing neurochemical models of information processing ability.
Ondo WG, Hunter C, Moore W
Neurology. 2004;62:37-40
Background: Injections of botulinum toxin A are an effective treatment for sialorrhea in Parkinson's disease (PD). Based on the relatively high rates of dry mouth seen with botulinum toxin B, there is reason to suspect that it may also improve sialorrhea.
Objective: To determine whether botulinum toxin B (Myobloc; Elan Pharmaceuticals, New York, NY) is a safe and effective treatment for sialorrhea in patients with PD.
Methods: Demographics, PD treatments, head posture, the Unified Parkinson's Disease Rating Scale (UPDRS), two questionnaires regarding drooling, Visual Analogue Scale, global impressions, salivary gland imaging, and a dysphagia questionnaire were assessed in 16 PD subjects with problematic sialorrhea. Patients were then randomized to receive either botulinum toxin B (1,000 units into each parotid gland and 250 units into each submandibular gland) or a pH-matched placebo, using only anatomic landmarks. Patients returned 1 month later to undergo an identical assessment.
Results: Compared with placebo, those randomized to drug reported improvement on the Visual Analogue Scale (p < 0.001), global impressions of change (p < 0.005), Drooling Rating Scale (p < 0.05), and Drooling Severity and Frequency Scale (p < 0.001). There was no change in UPDRS, head posture, or Dysphagia Scale. Adverse events were mild and included dry mouth (three patients), worsened gait (two), diarrhea (one), and neck pain (one) in the botulinum toxin B group.
Conclusion: Anatomically guided injections of botulinum toxin B into the parotid and submandibular glands appear to effectively improve sialorrhea without compromising dysphagia in patients with PD.
Kemoun G, Defebvre L, Watelain E, et al
Rev Neurol. 2003;159:1028-1037
Falls are a dramatic consequence of the age-related gait disorders. There are few prospective studies on falls predictive of the biomechanical features of gait. According to the literature, there are similarities between the gait observed in older people and in parkinsonian subjects. The objective of this study was to apply multiparametric gait analysis to demonstrate changes of the neuromotor gait pattern connected with falls. This prospective study included two groups of 16 subjects aged more than 60 years, who had not fallen during the previous year. One group included 16 minimally disabled parkinsonian patients off drugs, and the other group 16 healthy people. Gait recordings were obtained with a three-dimensional optoelectronic movement analysis system coupled with 2 force platforms in all persons who were followed for 1 year to collect data on all new events, particularly falls. Data analysis concerned spatiotemporal stride and three-dimensional power peaks developed in each lower limb joint. Cluster analysis of the 32 persons was used to determine various infraclinic neuromotor gait patterns. A post hoc analysis of variance was then applied to identify discriminating parameters. Three groups of subjects were identified with 3 different neuromotor gait patterns, independently of the presence of Parkinson disease. There were no fallers in first group (n=18). The second group (n=8) had 20 p.cent fallers and the third group (n=4) 100 p.cent fallers. The groups differed by 4 spatiotemporal parameters and 3 joint power peaks in the sagittal plane. Functional capacity was good in the first group with no falls recorded. This group of subjects had characteristics reported in the literature corresponding to a category of persons who compensate well for the phenomena of aging. Functional capacity was intermediary in the second group (20 p. cent were fallers). The kinematic pattern appeared to be less successful, revealing a tendency for stiff posture. The third group (100 p. cent fallers) exhibited inferior functional capacity. In this group, the kinematic pattern appeared to be disrupted. The subjects were unable to adapt satisfactorily to situations other than by stereotypical neuromotor reactions. In conclusion this study demonstrated a close determinism between physiological neuromotor aging and Parkinson's disease. The prospective follow-up demonstrated that falls that occurred were related to changes in neuromotor gait patterns. Three phases of gait pattern were also identified from minimal to major risk of falls.
Thomas A, Iacono D, Luciano AL, et al
J Neurol Neurosurg Psychiatry. 2004;75:141-143
Background: Recent short-term studies suggested that amantadine (Ama) might ameliorate dyskinesia in patients with Parkinson's disease. A double-blind study programmed over 12 months was designed to assess the duration of the antidyskinetic effect of amantadine on levodopa induced dyskinesia.
Methods: 40 patients treated for 7.5 (2.2) years with levodopa (729.3 (199.4) mg/day) and dopaminoagonists, having peak dose or dyphasic dyskinesia with or without pain, were assessed with the Unified Parkinson's Disease Rating Scale subscale IV, Items 32-34, the Dyskinesia Rating Scale and Investigator Global Assessment. Twenty patients received amantadine chloridrate (100 mg) and 20 received a placebo. The Ama or placebo could be withdrawn when scores indicated worsening of dyskinesia, after agreement with the patient.
Results: After 15 days of amantadine treatment there was a reduction by 45% in the total dyskinesia scores. All patients in the placebo group were withdrawn in 1-3 months and all patients in the Ama group were withdrawn in 3-8 months (p = 0.01, p<0.001). Ama withdrawal induced a rebound with increase of dyskinesia by 10-20% in 11 patients.
Conclusion: 300 mg amantadine reduces dyskinesia in Parkinson's disease by approximately 45% but the benefit lasted less than eight months.
Gorell JM, Peterson EL, Rybicki BA, Johnson CC
J Neurol Sci. 2004;217:169-174
Objective: To determine the relative contribution of various risk factors to the development of Parkinson's disease (PD).
Methods: Ten variables that were independently associated with PD in a health system population-based case-control study of epidemiological risk factors for the disease were jointly assessed. Stepwise logistic regression, adjusted for sex, race and age was used to develop a multiple variate model that best predicted the presence of PD. The population attributable risk was estimated for each variable in the final model, as well as for all factors together.
Results: The 10 initial variables included >20 years occupational exposure to manganese or to copper, individually; >20 years joint occupational exposure to either lead and copper, copper and iron, or lead and iron; a positive family history of PD in first- or second-degree relatives; occupational exposure to insecticides or herbicides; occupational exposure to farming; and smoking. Logistic regression resulted in a final model that included >20 years joint occupational exposure to lead and copper (p=0.009; population attributable risk [PAR]=3.9%), occupational exposure to insecticides (p=0.002; PAR=8.1%), a positive family history of PD in first- and second-degree relatives (p=0.001; PAR=12.4%), and smoking ≤30 pack-years or not smoking (p=0.005; PAR=41.4%). All four variables combined had a PAR=54.1%.
Conclusions: Our final model of PD risk suggests that occupational, environmental lifestyle and, likely, genetic factors, individually and collectively, play a significant role in the etiology of the disease. Clearly, additional risk factors remain to be determined through future research.
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