Kinect-based objective assessment of the acute levodopa challenge test in parkinsonism: a feasibility study.

INTRODUCTION: The acute levodopa challenge test (ALCT) is an important and valuable examination but there are still some shortcomings with it. We aimed to objectively assess ALCT based on a depth camera and filter out the best indicators. METHODS: Fifty-nine individuals with parkinsonism completed ALCT and the improvement rate (IR, which indicates the change in value before and after levodopa administration) of the Movement Disorder Society-Sponsored Revision of the Unified Parkinson's Disease Rating Scale part III (MDS-UPDRS III) was calculated. The kinematic features of the patients' movements in both the OFF and ON states were collected with an Azure Kinect depth camera. RESULTS: The IR of MDS-UPDRS III was significantly correlated with the IRs of many kinematic features for arising from a chair, pronation-supination movements of the hand, finger tapping, toe tapping, leg agility, and gait (rs = - 0.277 ~ - 0.672, P < 0.05). Moderate to high discriminative values were found in the selected features in identifying a clinically significant response to levodopa with sensitivity, specificity, and area under the curve (AUC) in the range of 50-100%, 47.22%-97.22%, and 0.673-0.915, respectively. The resulting classifier combining kinematic features of toe tapping showed an excellent performance with an AUC of 0.966 (95% CI = 0.922-1.000, P < 0.001). The optimal cut-off value was 21.24% with sensitivity and specificity of 94.44% and 87.18%, respectively. CONCLUSION: This study demonstrated the feasibility of measuring the effect of levodopa and objectively assessing ALCT based on kinematic data derived from an Azure Kinect-based system.

Parkinson's disease psychosis: symptoms, management, and economic burden.

Parkinson's disease psychosis (PDP) is a costly,debilitating condition that generally develops several years after diagnosis of Parkinson's disease (PD).PD is the second-most common neurodegenerative disease, and it imposes a significant burden on the healthcare system. Non-motor symptoms commonly manifest in PD, contributing to the severity of a patient's disability. The neuropsychiatric symptoms that are common in PD can be a significant source of distress to patients and caregivers. Recent studies have shown that more than 50% of patients with PD will develop psychosis at some time over the course of the disease. The responsibility for caring for a person with PDP frequently falls on family members. Caregiver distress is frequently predicted when patients with PD have symptoms of psychosis.Hallucinations and delusions are independent predictors of nursing home placement for patients with PDP. The authors sought to examine total healthcare expenditures among patients with PDP compared with patients with PD without psychosis.All costs were higher for patients with PDP than for those with PD without psychosis and all-Medicare cohorts, with the highest cost differentials found in long-term care costs ($31,178 for PDP vs $14,461 forPD without psychosis), skilled nursing facility costs($6601 for PDP vs $2067 for PD without psychosis),and inpatient costs ($10,125 for PDP vs $6024 for PD without psychosis). Patients with PDP spent an average of 179 days in long-term care, compared with 83 days for patients with PD without psychosis. As expected, long-term care utilization and expenditures were significantly higher for patients with PDP than for patients with PD without psychosis. Reducing long-term care utilization by patients with PDP may significantly lower the overall economic burden associated with PDP.

[Epidemiology of parkinsonism in the Guadalajara Health Area]. / Epidemiología del parkinsonismo en el Área de Salud de Guadalajara.

OBJECTIVES: 1) To determine the prevalence of Parkinson syndromes in the Guadalajara Health Area and its Basic Health Zones, as well as the typology of the Parkinson's disease; 2) to determine the distribution of antiparkinsonian medication use in the whole Area, and 3) to evaluate the cost per person and per year of this use according to the criteria of sex and age. MATERIAL AND METHOD: A descriptive cross-sectional study including 1,352 subjects affected by parkinsonism in the Guadalajara Area of both sexes and all ages. The variables measured were age, sex, environment, diagnosis, typology of the Parkinson's disease using the Hoehn and Yahr index, treatment, total cost and mean cost of the treatment per person per year. Prevalences were calculated, and the appropriate descriptive statistics were used. RESULTS: The prevalence of parkinsonism was 585/10(5) inhabitants, being higher in a rural environment (P<.05), in females (P<.01) and in subjects over 90 years (P<.01). The majority suffered from Parkinson's disease (P<.001), of whom 43.4% had symptoms equivalent to Yahr grade II (P<.001). The active ingredient most used was levodopa/carbidopa (51.3%) (P<.001) and the mean drug cost per person was 514.37€. CONCLUSIONS: The prevalence of parkinsonism is similar to that in the rest of the country, although in our study there is a predominance of females and it is in a rural environment. Levodopa is the drug most used, and the mean therapeutic cost per person is similar to the rest of Spain.

Prospective assessment of peripheral neuropathy in Duodopa-treated parkinsonian patients.

BACKGROUND: Although peripheral neuropathies (PN) have been described in patients with Parkinson's disease (PD) treated with oral dopaminergic therapies, anecdotal reports of subacute severe PN have been reported during treatment with enteral levodopa/carbidopa infusion (Duodopa). AIM OF THE STUDY: We prospectively assessed clinical and electrophysiological data of 15 consecutive patients with PD treated with Duodopa for a mean follow-up of 9 months. METHODS: Nerve conduction studies and a clinical evaluation with a standardized battery of peripheral neuropathy scales were performed at baseline and after a mean follow-up of 9 months. RESULTS: At baseline, mild signs of PN were observed in three subjects, and vitamin B12 serum levels were found to correlate with the amplitude of sural sensory action potentials. Follow-up data were available for 10/15 subjects: one patient developed a subacute sensory-motor PN and three subjects with pre-existing PN showed a moderate worsening of electrophysiological and clinical features. Subclinical electrophysiological alterations of peripheral nerves were observed in two subjects. No significant changes were observed in vitamin B12, folate, homocysteine and methylmalonic acid levels. CONCLUSIONS: In this consecutive series of patients treated with Duodopa, we observed one subacute sensory-motor PN and few length-dependent alterations of peripheral nerves, similar to those described during oral levodopa treatment.

Neurobehavioral assessment of hydroalcoholic extract of Trigonella foenum-graecum seeds in rodent models of Parkinson's disease.

CONTEXT: Neuroprotective therapy to rescue dopaminergic neurons is an important trait in the management of Parkinson's disease (PD). OBJECTIVE: The present study identified and evaluated SFSE-T, a standardized hydroalcoholic extract of Trigonella foenum-graecum L. seeds (Fabaceae), in animal models of PD. MATERIALS AND METHODS: The identification of SFSE-T was carried out by high-performance liquid chromatography for the marker compound trigonelline (TGN). The effects of single dose oral treatment of SFSE-T (10, 30 or 100 mg/kg) were studied using animal models of PD, namely, 6-hydroxydopamine (6-OHDA)-induced unilateral lesions in rats, and 4-phenyl-1,2,3,6-tetrahydropyridine (MPTP)-induced neurodegeneration in C57BL/6 mice. The effects of SFSE-T on monoamino oxidase (MAO) enzyme in vitro as well as possible side effects of SFSE-T in vivo were also evaluated. RESULTS: The concentration of TGN in a test sample of SFSE-T was found to be 82%. SFSE-T (30 mg/kg, oral) showed a significant increase in the number of ipsilateral rotations (45.67 rotations in 30-min period) as compared with vehicle control group (no rotations) when tested in 6-OHDA-induced unilateral lesioned rats. SFSE-T (30 mg/kg, oral) showed significant reversal of motor dysfunction (spontaneous motor activity scores, speed, distance traveled and number of square crossed) caused by MPTP induced lesions in C57BL/6 mice in pretreatment (1 h) schedule but not in post-treatment (1 h) schedule. SFSE-T neither showed anticholinergic effects nor showed selective MAO-B enzyme inhibition in vitro. DISCUSSION AND CONCLUSION: SFSE-T showed reversal of motor symptoms in an animal model of PD probably through neuroprotective properties.

Autonomic dysfunction in parkinsonian disorders: assessment and pathophysiology.

Parkinson's disease (PD) is a progressive neurodegenerative disorder characterised by motor dysfunction (parkinsonism) and several non-motor features. Dysautonomia is a significant non-motor feature as well as a neuropsychiatric symptom. Autonomic dysfunction can occur even in the early stages of PD, often preceding the onset of the classic motor symptoms of PD. The patterns of autonomic features in PD are different from other parkinsonian disorders. Detection of autonomic dysfunction may therefore be helpful in diagnosing PD in the early or pre-motor stages, and/or in differentiating it from other parkinsonian disorders, such as multiple system atrophy and progressive supuranuclear palsy. The aim of this review is to describe aspects of autonomic dysfunction, including symptoms, assessment and pathophysiology, resulting from autonomic impairment in PD and other parkinsonian syndromes.

Atypical antipsychotic use and risk of fracture in persons with Parkinsonism.

Our objective was to estimate the effect of atypical antipsychotics (AAs) on the rate of fractures in a parkinsonism population. We conducted an age- and state-matched nested case-control study in five states (CA, FL, NY, OH, IL) using the Medicaid analytic extract from 2001 to 2002. Eligible participants had a diagnosis of parkinsonism, excluding persons with secondary parkinsonism, bone cancer, bone infections, schizophrenia, schizoaffective disorder, and those who used conventional antipsychotics. The primary outcome was the occurrence of a fracture of the femur, ankle, fibula, tibia, humerus, radius, or ulna (N = 851). Risk-set sampling defined controls (N = 4220). We used conditional-logistic regression to derive adjusted odds ratios (AOR) and 95% confidence intervals of the association between fracture and use of quetiapine, risperidone, or olanzapine in the 60 days before the index date compared to nonuse. After adjustment for confounding, use of quetiapine (AOR 2.4; 95% CI 1.5-3.8), risperidone (AOR 1.2; 95% CI 0.9-1.7), or olanzapine (AOR 1.7; 95% CI 1.2-2.4) was associated with a higher rate of fracture. Use of an AA was associated with a higher rate of fracture in persons with parkinsonism. Prescribers must be cautious when using these agents in elderly persons with parkinsonism.

Review of the therapeutic management of Parkinson's disease. Report of a joint task force of the European Federation of Neurological Societies and the Movement Disorder Society-European Section. Part I: early (uncomplicated) Parkinson's disease.

The aim of the study was to provide evidence-based recommendations for the management of early (uncomplicated) Parkinson's disease (PD), based on a review of the literature. Uncomplicated PD refers to patients suffering from the classical motor syndrome of PD only, without treatment-induced motor complications and without neuropsychiatric or autonomic problems. MEDLINE, Cochrane Library and International Network of Agencies for Health Technology Assessment (INAHTA) database literature searches were conducted. National guidelines were requested from all European Federation of Neurological Societies (EFNS) societies. Non-European guidelines were searched for using MEDLINE. Part I of the guidelines deals with prevention of disease progression, symptomatic treatment of motor features (parkinsonism), and prevention of motor and neuropsychiatric complications of therapy. For each topic, a list of therapeutic interventions is provided, including classification of evidence. Following this, recommendations for management are given, alongside ratings of efficacy. Classifications of evidence and ratings of efficacy are made according to EFNS guidance. In cases where there is insufficient scientific evidence, a consensus statement (good practice point) is made.

Drugs in development for Parkinson's disease: an update.

The current development of emerging pharmacological treatments for Parkinson's disease (PD), front preclinical to launch, is summarized. Advances over the past year are highlighted, including the significant progress of several drugs through various stages of development. Several agents have been discontinued from development, either because of adverse effects or lack of clinical efficacy. The methyl-esterified form of L-DOPA (melevodopa) and the monoamine oxidase type B inhibitor rasagiline have both been launched. With regard to the monoamine re-uptake inhibitors, many changes have been witnessed, with new agents reaching preclinical development and pre-existing ones being discontinued or having no development reported. Of the dopamine agonists, many continue to progress successfully through clinical trials. Others have struggled to demonstrate a significant advantage over currently available treatments and have been discontinued. The field of non-dopaminergic treatments remains dynamic. The alpha2 adrenergic receptor antagonists and the adenosine A2A receptor antagonists remain in clinical trials. Trials of the neuronal' synchronization modulator levetiracetam are at an advanced stage, and there has also been a new addition to the class (ie, seletracetam). There has been a change in the landscape of neuroprotective agents that modulate disease progression. Candidates from the classes of growth factors and glyceraldehyde-3-phosphate dehydrogenase inhibitors have been discontinued, or no development has been reported, and the mixed lineage kinase inhibitor CEP-1347 has been discontinued for PD treatment. Other drugs in this field, such as neuroimmunophilins, estrogens and alpha-synuclein oligomerization inhibitors, remain in development.

[Utility of 123-I ioflupane SPECT in the assessment of patients with Parkinsonian syndrome and cerebral vasculopathy]. / SPECT con ioflupano I-123 en la catalogación de pacientes con síndrome parkinsoniano y vasculopatía cerebral.

OBJECTIVE: To assess the utility of 123-I Ioflupane SPECT (IS) in the identification of the origin of Parkinsonism (vascular or idiopathic) in patients with cerebral vasculopathy (CV) demonstrated by morphological imaging techniques. Also, to assess the therapeutic impact. MATERIALS AND METHODS: 42 patients (16 males and 26 females) with a Parkinsonian syndrome were studied. Average age was 78.7 years (50-88). A dose of 185 MBq of 123 I-Ioflupane was injected in all subjects. SPECT imaging was obtained 5 hours later. All patients had a CT and/or MRI. The final diagnoses, after a minimal follow-up of 12 months, was established by a neurologist expert in movement disorders, based on clinical and imaging features and response to treatment. RESULTS: 14 patients were diagnosed of functional vascular Parkinsonism by alteration of association pathways, 3 of structural vascular Parkinsonism (SVP) with anatomical and functional vascular lesion in striatum, 14 of Parkinson's disease (PD) with CV, 2 of mixed Parkinsonism (PD + SVP) and 9 with others diagnoses different to the previous. The result of IS changed the treatment in 7/42 patients. CONCLUSION: The IS can have a complementary role to clarify the etiology of Parkinsonism in patients with cerebral vasculopathy. Interpretation of functional and anatomical images within the clinical context of each patient is necessary.

Parkinsonism in multiple system atrophy: natural history, severity (UPDRS-III), and disability assessment compared with Parkinson's disease.

We analyzed parkinsonian features in multiple system atrophy (MSA) compared with age- and disease duration-matched Parkinson's disease (PD) patients, and assessed the applicability of the Unified Parkinson's Disease Rating Scale (UPDRS) -III motor scale as a means of rating their severity. Cross-sectional analysis of parkinsonism was done using UPDRS-III, International Cerebellar Atatia Rating Scale, and disability scales (Hoehn and Yahr [H&A], Schwab and England, Katz and Lawton) in 50 unselected MSA patients and in 50 matched PD patients. At symptom onset, falls occurred 10 times more frequently in MSA, whereas limb tremor was 10 times more common in PD. At first visit (10.2 months), hemiparkinsonism and pill-rolling rest tremor were less common in MSA. Hypomimia, atypical rest, postural or action tremor, as well as postural instability were more frequent in MSA. At study examination (62.4 months), parkinsonian signs in MSA patients were more frequently symmetrical and associated with axial rigidity, antecollis and postural instability. A levodopa response of >50% was seen in <10% of MSA patients. Modified H&Y stages (3.2 +/- 1.3 vs. 2.2 +/- 0.78) and UPDRS-III scores (48.14 +/- 19.5 vs. 31.74 +/- 12.9) were significantly (P = 0.0001) higher in MSA. The internal consistency of the UPDRS-III was fair in MSA patients (Cronbach's alpha >0.90), and correlated well with marked dependency on the Schwab and England and Katz and Lawton scales. Factor structure analysis of UPDRS-III in MSA showed five clinically distinct subscores accounting for 74% of the variance, differing from PD by the dependency of the face-speech and limb bradykinesia items and independence of the postural-action tremor from the rest tremor items. There was a significant correlation (R(2) = 0.70, P = 0.001) between ICARS ataxia and UPDRS-III scores in MSA patients. Results confirm a distinct profile of parkinsonism in MSA and greater severity and disability compared with PD. It also indicates that the UPDRS-III provides a useful severity measure of parkinsonism in MSA, albeit contaminated by additional cerebellar dysfunction.

Assessment of motor behavior using a video system and a clinical rating scale in parkinsonian monkeys lesioned by MPTP.

The best current model of Parkinson's disease is the primate treated with 1-methyl-4-phenyl-1,2,3,6-tetrahydropyridine (MPTP). Quantification of animal movement is important for the study of severity of parkinsonian syndrome induced by MPTP and response to drug treatments. Both require clinical rating scales that measure motor behavior with well-defined objective items. However, evaluations using these scales depend on the observer scoring the different items, according to his/her experience. The video image analyzer system, which produces an activity curve in correlation with the visual study of animal motor behavior, offers an automatic evaluation method that is observer-independent and reproducible. Using such an system we defined items correlated with those used in clinical rating scales that are sensitive to animal motor changes, decrease in movements with MPTP intoxication and alleviation afforded by levodopa: global locomotor activity and specific activities (climbing, social interactions, eating and drinking behaviors).

Costs in the treatment of parkinsonism.

Parkinson's disease imposes a considerable economic burden on our society. Apart from the direct costs for therapy, the indirect costs of the disease are estimated to be substantially higher. Unfortunately, only the high costs of current medication are usually considered, when financial aspects are discussed. An ideal therapy should ameliorate the symptoms of the disease and achieve a high quality of life. but the prognosis should also be improved. Cost estimates have to be extended throughout the course of the disease. We recommend a treatment schedule which is expected to result in a favorable cost profile when the entire course of the disease, is considered. L-Dopa monotherapy in working patients is obsolete. During the course of the disease dopamine agonists, amantadine, budipine, COMT inhibitors and selegiline will be used.