Advanced Stages Of Parkinson's Disease Research Articles

GC and VDR SNPs and Vitamin D Levels in Parkinson's Disease: The Relevance to Clinical Features.

Vitamin D deficiency is suggested to be associated with Parkinson's disease (PD). Our aim was to investigate the serum 25-hydroxyvitamin D3 (25OHD) levels of PD patients in Turkish cohort, to investigate any association of vitamin D binding protein (GC) genotypes with PD due to the significant role of GC in vitamin D transport, to determine whether vitamin D receptor (VDR) haplotype that we previously demonstrated to be a risk haplotype for AD is also a common haplotype for PD and to investigate any relevant consequence of serum 25OHD levels, GC or VDR genotypes on clinical features of PD. Three hundred eighty-two PD patients and 242 healthy subjects were included in this study. The serum 25OHD levels were investigated by CLIA, and GC and VDR SNPs were evaluated with LightSnip. Our results indicated a strong relationship between low serum 25OHD levels and PD (p<0.001). rs7041 of GC and ApaI of VDR were associated with the PD risk (p<0.05). Minor allele carriers for BsmI of VDR gene in both PD patients and healthy subjects had significantly higher levels of serum 25OHD (p<0.05). The homozygous major allele carriers for rs2282679, rs3755967 and rs2298850 of GC gene in PD patients with slower progression had significantly higher levels of serum 25OHD (p<0.05). Minor allele carriers for FokI of VDR gene were more frequent in patients with advanced-stage PD (p<0.05). Consequently, this is the first study demonstrating GC gene as a risk factor for PD. The relationship between PD's clinical features and low 25OHD or risk genotypes might have effects on PD independently.

Amide proton transfer MR imaging at 3. 0 T of the basal ganglia in Parkinson's disease

Objective To explore the feasibility of amide proton transfer (APT) MR imaging for the detection of basal ganglia abnormalities in patients with Parkinson's disease (PD). Methods Twenty-seven patients with PD and twenty-three age-matched normal control subjects underwent cerebral APT and structural MR imaging. The magnetic resonance ratio asymmetry (MTRasym) values at 3.5 ppm of bilateral globus pallidus, putamen and caudate were measured on APT images. MTRasym (3.5 ppm) values of cerebral structures between PD patients and control subjects were compared with independent-samples t test. Paired-samples t test was used to compare the difference of MTRasym (3.5 ppm) between the side of onset and contralateral side in patients with PD. The difference of MTRasym (3.5 ppm) among normal controls, early-stage PD, and advanced-stage PD patients was assessed with one-way analysis of variance. Results Compared to normal controls, MTRasym (3.5 ppm) values of globus pallidus, putamen and caudate were significantly increased in PD patients ((0.89±0.12)% vs (0.57±0.16)%, (1.05±0.11)% vs (0.82±0.15)%, (1.15±0.13)% vs (0.78±0.19)%; t=3.311, 2.562, 3.277 respectively, all P values <0.05). Significant differences in MTRasym (3.5 ppm) values of these cerebral structures were observed among normal controls, early-stage PD and advanced-stage PD patients. And MTRasym (3.5 ppm) values in globus pallidus, putamen and caudate were significantly higher in early-stage PD patients than normal controls. In PD patients, even not statistically significant, MTRasym (3.5 ppm) values of sides of onset were slightly lower than contralateral sides. Conclusions APT MR imaging can sensitively identify the difference of MTRasym (3.5 ppm) in the basal ganglia between PD patients and normal controls. APT might be a useful tool to evaluate abnormal metabolite in basal ganglia of PD patients. Key words: Parkinson disease; Basal ganglia; Magnetic resonance imaging; Amide proton transfer

Assessment of striatal & postural deformities in patients with Parkinson's disease.

Background & objectives:Though striatal and postural deformities are known to occur commonly in atypical Parkinsonism patients, these may also be seen in patients with Parkinson's disease (PD). These are frequently misdiagnosed as joint or orthopaedic pathology leading to unnecessary investigations. This study was conducted to observe the various striatal and postural deformities among patients with PD in India.Methods:This study was conducted at a tertiary care teaching institute in north# India. Seventy consecutive patients with PD diagnosed as per the modified UK Brain Bank criteria were included. Various striatal (hand & foot) and postural (antecollis, camptocormia, scoliosis & Pisa syndrome) deformities and their relation with the duration of disease, severity [measured by the Unified Parkinson's Disease Rating Scale (UPDRS)] and levodopa intake were analyzed.Results:Of the 70 patients with PD, 34 (48.57%) had either striatal or postural deformities. Striatal foot was the most common deformity observed (25.71%). Camptocormia was the second most common deformity (20%). Striatal and postural deformities were seen in more advanced PD as suggested by significantly higher UPDRS and Hoehn and Yahr scale (P<0.001). Striatal deformities were more ipsilateral to PD symptom onset side (agreement 94.44%). Pisa and scoliosis concavity were more on contralateral side to PD symptoms onset side (66.67%).Interpretation & conclusions:Our results showed that striatal and postural deformities were common and present in about half of the patients with PD. These deformities we more common in patients with advanced stage of PD.

Device-aided therapies in advanced Parkinson's disease

Advanced stages of Parkinson's disease (PD) is a consequence of the severe neurodegenerative process and are characterized by the development of motor fluctuations and dyskinesia, aggravation of non-motor symptoms. Treatment with peroral and transdermal drugs can't provide an adequate control of PD symptoms and quality-of-life of the patients at this stage of disease. Currently, three device-aided therapies: deep brain stimulation (DBS), intrajejunal infusion of duodopa, subcutaneous infusion of apomorphine can be used in treatment of patients with advanced stages of PD. Timely administration of device-aided therapies and right choice of the method determine, to a large extent, the efficacy and safety of their use. Despite the high efficacy of all three methods with respect to the fluctuation of separate symptoms, each method has its own peculiarities. The authors reviewed the data on the expediency of using each method according to the severity of motor and non-motor symptoms, patient's age, PD duration, concomitant pathology and social support of the patients.

Análisis cuantitativo de la marcha en pacientes con enfermedad de Parkinson avanzada

To describe the gait disorders and postural instability in a group of patients with advanced Parkinson's disease (PD). Gait was analysed in patients in advanced stages of PD on medication. Using a computerised analysis system, we studied the kinematic variables: cadence, number of correct gait cycles (HFPS cycles), total number of cycles, duration of the phases of the cycle, electromyography and a goniometric study of the knee and the ankle. The clinical appraisal of balance and postural instability was completed with the Tinetti and Timed Up and Go tests. The analysis showed alterations in the spatio-temporal parameters with respect to the ranges considered to be normal: reduction of the HFPS cycles, increase in the total number of cycles and alteration of the cadence in many patients. It also revealed that the mean cadence was kept within the limits of normal values, an increase in the duration of the contact phase, reduction of monopodal support and alteration of the joint range of motion of the knee and the ankle. Likewise, changes are also observed in the scores obtained on the clinical scales, which show an increase in the risk factor for falls and mild dependence. Quantification by objective analysis of the kinetic and kinematic variables in patients with PD can be used as a tool to establish the influence of the different therapeutic alternatives in gait disorders.

Pathophysiology of Motor Dysfunction in Parkinson's Disease as the Rationale for Drug Treatment and Rehabilitation.

Cardinal motor features of Parkinson's disease (PD) include bradykinesia, rest tremor, and rigidity, which appear in the early stages of the disease and largely depend on dopaminergic nigrostriatal denervation. Intermediate and advanced PD stages are characterized by motor fluctuations and dyskinesia, which depend on complex mechanisms secondary to severe nigrostriatal loss and to the problems related to oral levodopa absorption, and motor and nonmotor symptoms and signs that are secondary to marked dopaminergic loss and multisystem neurodegeneration with damage to nondopaminergic pathways. Nondopaminergic dysfunction results in motor problems, including posture, balance and gait disturbances, and fatigue, and nonmotor problems, encompassing depression, apathy, cognitive impairment, sleep disturbances, pain, and autonomic dysfunction. There are a number of symptomatic drugs for PD motor signs, but the pharmacological resources for nonmotor signs and symptoms are limited, and rehabilitation may contribute to their treatment. The present review will focus on classical notions and recent insights into the neuropathology, neuropharmacology, and neurophysiology of motor dysfunction of PD. These pieces of information represent the basis for the pharmacological, neurosurgical, and rehabilitative approaches to PD.

Wirelessly programmed deep brain stimulation of the bilateral subthalamic nucleus for the treatment of primary Parkinson′s disease: study protocol for a multicenter, randomized, parallel-controlled optimal-efficiency trial

Background: Deep brain stimulation (DBS) is a commonly used neurosurgical approach for the debilitating motor symptoms of Parkinson's disease (PD). A number of neurostimulation products have been developed, including the Medtronic implantable neurostimulator (Medtronic USA, Inc., USA) and a wirelessly programmed implantable neurostimulator (Sceneray Co. Ltd., China) with protection by independent intellectual property rights in China. This study will validate the safety and efficacy of implantable neurostimulators in the treatment of primary PD. Methods/Design: This is a prospective, single-blind, randomized parallel-controlled optimal-efficiency trial, which will be performed in five research centers. Sixty-four patients with middle-stage and advanced-stage idiopathic PD will be randomly assigned to an experimental group and a control group according to a 1:1 ratio. An implantable neurostimulator will be implanted in each participant in both groups, but the stimulator will be activated within 1 month of surgery in the experimental group, while the patients in the control group will not receive stimulation until 3 months after implantation. After 3 months, patients in both groups will receive stimulation from the implanted neurostimulator. Beginning 6 hours after implantation, all participants will receive anti-PD drugs such as dopamine receptor agonists and compound levodopa. The primary outcome measure in this study will be changes in motor function score (Unified Parkinson's Disease Rating Scale (UPDRS)-III), relative to the baseline value, in patients from each group upon withdrawal of medications for 12 hours at 3 months after surgery. The secondary outcome measures for this study include (1) changes in UPDRS-I, II, III, and IV scores in patients from each group under the influence of medication at 3, 6, 9, and 12 months after surgery relative to baseline values; (2) changes in UPDRS-III scores upon withdrawal of medications 12 months after surgery in stimulation on and off modes relative to baseline value; (3) patient satisfaction. Safety indices are the numbers and incidences of adverse events. Discussion: This study is the first to investigate the safety and efficacy of a wirelessly programmed implantable neurostimulator enforced with protection by independent intellectual property rights in China through a randomized controlled trial. If safe and effective outcomes are acquired, this implantable neurostimulator will become a new option for treatment of PD patients. Trial registration: This trial was registered at http://www.chictr.org.cn (registration number ChiCTR-INR-16008951) on 1 August 2016. Ethics: The study protocol has been approved by the Ethics Committee of Tangdu Hospital of the Fourth Military Medical University of China (approval number: 2012009); Ethics Committee of Changhai Hospital of China (approval number: CHEC2012-044); Clinical Trial Ethics Committee, Ruijin Hospital, Shanghai Jiao Tong University School of Medicine of China (approval number: 2012-67); Clinical Trial and Biomedical Ethics Committee of West China Hospital of Sichuan University of China (approval number: 2012-7); Ethics Committee of First Affiliated Hospital of Guangzhou Medical University of China (approval number: 2013-8). The study protocol will be performed in strict accordance with the Declaration of Helsinki, formulated by the World Medical Association. Informed consent: Signed informed consent will be obtained from the patients or their relatives.

Chemical Exchange Saturation Transfer MR Imaging is Superior to Diffusion-Tensor Imaging in the Diagnosis and Severity Evaluation of Parkinson's Disease: A Study on Substantia Nigra and Striatum.

Parkinson’s disease (PD) is a neurodegenerative disorder characterized by nigrostriatal cell loss. To date, the diagnosis of PD is still based primarily on the clinical manifestations, which may be typical and obvious only in advanced-stage PD. Thus, it is crucial to find a reliable marker for the diagnosis of PD. We conducted this study to assess the diagnostic efficiency of chemical exchange saturation transfer (CEST) imaging and diffusion-tensor imaging (DTI) in PD at 3 T by evaluating changes on substantia nigra and striatum. Twenty-three PD patients and twenty-three age-matched normal controls were recruited. All patients and controls were imaged on a 3-T MR system, using an eight-channel head coil. CEST imaging was acquired in two transverse slices of the head, including substantia nigra and striatum. The magnetization transfer ratio asymmetry at 3.5 ppm, MTRasym(3.5 ppm), and the total CEST signal intensity between 0 and 4 ppm were calculated. Multi-slice DTI was acquired for all the patients and normal controls. Quantitative analysis was performed on the substantia nigra, globus pallidus, putamen, and caudate. The MTRasym(3.5 ppm) value, the total CEST signal intensity, and fractional anisotropy value of the substantia nigra were all significantly lower in PD patients than in normal controls (P = 0.003, P = 0.004, and P < 0.001, respectively). The MTRasym(3.5 ppm) values of the putamen and the caudate were significantly higher in PD patients than in normal controls (P = 0.010 and P = 0.009, respectively). There were no significant differences for the mean diffusivity in these four regions between PD patients and normal controls. In conclusion, CEST MR imaging provided multiple CEST image contrasts in the substantia nigra and the striatum in PD and may be superior to DTI in the diagnosis of PD.

The contribution of white matter lesions (WML) to Parkinson's disease cognitive impairment symptoms: A critical review of the literature

We reviewed the impact of white matter lesions (WML) of cerebrovascular origin on cognitive impairment in Parkinson's disease (PD) patients. A search of PUBMED and Googlescholar.com revealed eleven studies that met the inclusion criteria: diagnosis based on the United Kingdom Brain Bank criteria (UK BBC); cognitive assessment; WML assessed on magnetic resonance imaging (MRI) by semiquantitative visual scales or automated method.Eight studies described the negative impact of WML on cognition in PD. Patients with mild cognitive impairment (MCI) and dementia had significantly more WML than the group without MCI and dementia. There was significant relationship between increasing total WML volume and worse performance on executive function, memory and language. Patients with vascular parkinsonism and dopaminergic denervation had more severe frontal lobe dysfunctions than patients with PD. In contrast in three studies there was no negative correlation between WML and cognition. Although the progression of neurodegenerative process in advanced stage of PD has been recognized as being mainly responsible for cognitive impairment in PD, WML may also be a contributing factor. It is possible that by reducing the vascular risk factors that cause WML cognitive impairment could be prevented or slowed down.

The effect of tremor onset on middle cerebellar peduncle of Parkinson's disease

The majority of studies of Parkinson's disease (PD) focused on basal ganglia initially; however, accumulating evidence suggests cerebellar involvement in pathophysiology. We aimed to investigate the effects of tremor onset on middle cerebellar peduncle (MCP) width of PD patients and of disease duration on differential diagnosis. We measured MCP width of 81 PD, 34 multiple system atrophy (MSA) and 16 normal controls, using MRI. A meta-analysis was performed including two previous and the present studies. We carried out correlation analysis between disease duration and MCP width separately in subgroup of PD with or without tremor onset. Receiver operating characteristic curves were analyzed. Our meta-analysis indicated that MCP width was significantly smaller in MSA relative to PD with homogeneous studies. There was significant correlation between disease duration and MCP width in PD without tremor onset. In contrast, there was no correlation observed in PD with tremor onset. Subclassification according to disease duration showed improved area under curve of PD vs. MSA with predominant parkinsonian features. MCP width could be a valuable tool for differential diagnosis. Our finding suggested that MCP was impaired in advanced stage of PD without tremor onset as part of the abnormality of the cerebellar system.

Levodopa-induced plasticity: a double-edged sword in Parkinson's disease?

The long-term replacement therapy with the dopamine (DA) precursor 3,4-dihydroxy-l-phenylalanine (L-DOPA) is a milestone in the treatment of Parkinson's disease (PD). Although this drug precursor can be metabolized into the active neurotransmitter DA throughout the brain, its therapeutic benefit is due to restoring extracellular DA levels within the dorsal striatum, which lacks endogenous DA as a consequence of the neurodegenerative process induced by the disease. In the early phases of PD, L-DOPA treatment is able to restore both long-term depression (LTD) and long-term potentiation (LTP), two major forms of corticostriatal synaptic plasticity that are altered by dopaminergic denervation. However, unlike physiological DA transmission, this therapeutic approach in the advanced phase of the disease leads to abnormal peaks of DA, non-synaptically released, which are supposed to trigger behavioural sensitization, namely L-DOPA-induced dyskinesia. This condition is characterized by a loss of synaptic depotentiation, an inability to reverse previously induced LTP. In the advanced stages of PD, L-DOPA can also induce non-motor fluctuations with cognitive dysfunction and neuropsychiatric symptoms such as compulsive behaviours and impulse control disorders. Although the mechanisms underlying the role of L-DOPA in both motor and behavioural symptoms are still incompletely understood, recent data from electrophysiological and imaging studies have increased our understanding of the function of the brain areas involved and of the mechanisms implicated in both therapeutic and adverse actions of L-DOPA in PD patients.

Advanced stages of PD: interventional therapies and related patient-centered care.

During the last decades, symptomatic treatment of motor symptoms of Parkinson's disease (PD) improved continuously and is reflected by long-range independency of the patient during the disease course. However, advanced stages of PD still represent an important challenge to patients, caregivers and treating physicians. In patients with advanced PD, interventional therapy strategies are increasingly applied. These device-related treatment strategies using pump-based continuous dopaminergic stimulation (CDS) or deep brain stimulation (DBS) opened new treatment options especially if motor complications predominate. Well-designed clinical studies on these interventional therapeutic approaches provided class 1 evidence for the efficacy of DBS and CDS in advanced PD and opened new perspectives for their use in earlier disease stages also. Therefore, careful selection of patients amenable to the (semi)invasive therapy options becomes more and more important and requires an interdisciplinary setting that accounts for (i) optimal patient information and awareness, (ii) selection of best individual treatment modality, (iii) training of relatives and caregivers, (iv) management of complications, and (v) follow-up care. Here, we address these topics by summarizing current state-of-the-art in patient selection, providing specificities of treatment options and troubleshooting, and defining steps towards an optimized patient-centered care. Interventional therapies pioneer in the area of individualized treatment approaches for PD, and may be complemented in the future by biomarker-based improved stratification and by closed-loop systems for adaptive therapeutic strategies. In the present review, we summarize the proceedings of an Expert Workshop on Parkinson's disease held on November 22, 2014 in Frankfurt, Germany.

The impact of clinical symptoms on quality of life in patients with advanced stage Parkinson's disease and their caregivers (P6.059)

The impact of clinical symptoms on quality of life in patients with advanced stage Parkinson's disease and their caregivers (P6.059)

An update on pharmacological, pharmacokinetic properties and drug-drug interactions of rotigotine transdermal system in Parkinson's disease and restless legs syndrome.

This narrative review reports on the pharmacological and pharmacokinetic properties of rotigotine, a non-ergolinic D3/D2/D1 dopamine receptor agonist approved for the treatment of early- and advanced-stage Parkinson’s disease (PD) and moderate to severe restless legs syndrome (RLS). Rotigotine is formulated as a transdermal patch providing continuous drug delivery over 24 h, with a plasma concentration profile similar to that of administration via continuous intravenous infusion. Absolute bioavailability after 24 h transdermal delivery is 37 % of the applied rotigotine dose. Following a single administration of rotigotine transdermal system (24-h patch-on period), most of the absorbed drug is eliminated in urine and feces as sulphated and glucuronidated conjugates within 24 h of patch removal. The drug shows a high apparent volume of distribution (>2500 L) and a total body clearance of 300–600 L/h. Rotigotine transdermal system provides dose-proportional pharmacokinetics up to supratherapeutic dose rates of 24 mg/24 h, with steady-state plasma drug concentrations attained within 1–2 days of daily dosing. The pharmacokinetics of rotigotine transdermal patch are similar in healthy subjects, patients with early- or advanced-stage PD, and patients with RLS when comparing dose-normalized area under the plasma concentration–time curve (AUC) and maximum plasma drug concentration (C max), as well as half-life and other pharmacokinetic parameters. Also, it is not influenced in a relevant manner by age, sex, ethnicity, advanced renal insufficiency, or moderate hepatic impairment. No clinically relevant drug–drug interactions were observed following co-administration of rotigotine with levodopa/carbidopa, domperidone, or the CYP450 inhibitors cimetidine or omeprazole. Also, pharmacodynamics and pharmacokinetics of an oral hormonal contraceptive were not influenced by rotigotine co-administration. Rotigotine was generally well tolerated, with an adverse event profile consistent with dopaminergic stimulation and use of a transdermal patch. These observations, combined with the long-term efficacy demonstrated in clinical studies, support the use of rotigotine as a continuous non-ergot D3/D2/D1 dopamine receptor agonist in the treatment of PD and RLS.

Characterization of gastrointestinal disorders in patients with parkinsonian syndromes.

This study was aimed to investigate gastrointestinal (GI) dysfunction in patients with Parkinson's disease (PD) compared with those in patients with other parkinsonian disorders, and to characterize parkinsonian motor and non-motor correlates for GI dysfunction. Consecutive patients with PD, atypical parkinsonism (P-plus) and vascular parkinsonism (VP) were enrolled in this multicenter systematic survey. Data for weight loss, appetite loss, sialorrhea, dysphagia, gastroesophageal reflux disease (GERD) and constipation were simultaneously collected using symptom-specific, structured questionnaires. For the PD group, information for onset age, PD duration, anti-parkinsonian drug dosages, unified PD rating scale, and Hoehn & Yahr stage were collected at the time of the interview. Enrolled in the study were 329 PD, 82P-plus, and 62 VP patients. GI symptom frequencies were similar in PD and other parkinsonian groups. Among the PD patients, constipation was the most common symptom, followed by appetite loss, weight loss, dysphagia, sialorrhea, and GERD (64.9%, 45.4%, 35.7%, 19.4%, 15.0%, and 9.6%, respectively). Dysphagia, sialorrhea, and constipation became more frequent with more advanced PD stages. Cognition, sleep and mood disturbances were significantly associated with weight loss, appetite loss, and dysphagia, whereas bradykinesia, axial and postural instability with gait disturbance were associated with dysphagia. GI disturbance is common in patients with non-PD parkinsonism as well as in those with PD. GI symptoms correlated with distinct parkinsonian motor and nonmotor features in PD. Further studies are warranted to reveal the pathophysiological mechanisms and prognostic features of GI disturbances in parkinsonian disorders.

Pramipexole in Parkinson's disease

Pramipexole is non-ergoline dopamine receptor agonist. There is accumulating evidence for the efficacy of pramipexole in treatment of Parkinson's disease (PD). Authors have summarized the results concerning the optimal start treatment, the using of pramipexole in early and advanced PD stages, effects of pramipexole on tremor, cognitive impairment, affective functions and safety pramipexole.

Rotigotine vs ropinirole in advanced stage Parkinson's disease: a double-blind study.

To confirm the superiority of transdermal rotigotine up to 16mg/24h over placebo, and non-inferiority to ropinirole, in Japanese Parkinson's disease (PD) patients on concomitant levodopa therapy. This trial was a randomized, double-blind, double-dummy, three-arm parallel group placebo- and ropinirole-controlled trial. Four-hundred and twenty PD patients whose motor symptoms were not well controlled by levodopa treatment were randomized 2:2:1 to receive rotigotine, ropinirole (up to 15mg/day) or placebo during a 16-week treatment period followed by a 4-week taper period. The primary variable was change in the Unified Parkinson's Disease Rating Scale (UPDRS) Part III (ON state) sum score from baseline to the end of the treatment period. The difference in the change in the UPDRS Part III (ON state) sum score from baseline to the end of treatment between rotigotine and placebo groups was-6.4±1.2 (95% CI:-8.7 to-4.1; p<0.001), indicating superiority of rotigotine over placebo. The difference between rotigotine and ropinirole groups was-1.4±1.0 (95% CI:-3.2 to 0.5), below the non-inferiority margin, indicating the non-inferiority of rotigotine to ropinirole. Application site reaction was seen in 57.7% of the patients in the rotigotine group and in 18.6% in the ropinirole group (P<0.001). No other safety issue was noted. Rotigotine was well tolerated at doses up to 16mg/24h and showed similar efficacy to ropinirole except that the application site reaction was much higher in the rotigotine group.

Real life cost and quality of life associated with continuous intraduodenal levodopa infusion compared with oral treatment in Parkinson patients.

Advanced-stage Parkinson's disease (PD) strongly affects quality of life (QoL). Continuous intraduodenal administration of levodopa (IDL) is efficacious, but entails high costs. This study aims to estimate these costs in routine care. 10 patients with advanced-PD who switched from oral medication to IDL were assessed at baseline, and subsequently at 3, 6, 9 and 12 months follow-up. We used the Unified PD Rating Scale (UPDRS) for function and 15D for Quality of Life (QoL). Costs were assessed using quarterly structured patient questionnaires and hospital registries. Costs per quality adjusted life year (QALY) were estimated for conventional treatment prior to switch and for 1-year treatment with IDL. Probabilistic sensitivity analysis was based on bootstrapping. IDL significantly improved functional scores and was safe to use. One-year conventional oral treatment entailed 0.63 QALY while IDL entailed 0.68 (p > 0.05). The estimated total 1-year treatment cost was NOK419,160 on conventional treatment and NOK890,920 on IDL, representing a cost of NOK9.2 million (€1.18 mill) per additional QALY. The incremental cost per unit UPDRS improvement was NOK25,000 (€3,250). Medication was the dominant cost during IDL (45% of total costs), it represented only 6.4% of the total for conventional treatment. IDL improves function but is not cost effective using recommended thresholds for cost/QALY in Norway.

Sensorimotor connectivity in Parkinson's disease: the role of functional neuroimaging.

The diagnosis of Parkinson’s disease (PD) remains still clinical; nevertheless, in the last decades, the rapid evolution of advanced MRI techniques has made it possible to detect structural and, increasingly, functional brain changes in patients with PD. Indeed, functional MRI (fMRI) techniques have offered the opportunity to directly measure the brain’s activity and connectivity in patients with PD both in early and complicated stage of the disease. The aims of the following review are (1) to present an overview of recent fMRI reports investigating the activity and connectivity of sensorimotor areas in patients with PD using both task-related and “resting-state” fMRI analysis (2) to elucidate potential pathophysiological mechanisms underlying dyskinetic motor complications in the advanced stage of PD.

An Elderly Parkinsonian Patient with Extreme Blood Pressure Fluctuations

Blood pressure (BP) fluctuations after long-term levodopa therapy are rarely reported. Patients with Parkinson's disease (PD) often have dysautonomia, and neuropsychiatric and sleep disorders, which influence BP. It is difficult to control BP when hypertension coexists with these complications. We present the case of a 78-year-old man with PD who had hypotensive shock and extreme fluctuations of BP. Fluctuations in BP with the use of levodopa are more significant in patients with motor symptom fluctuations, autonomic nervous system disorders, primary hypertension, advanced stage of PD, and anxiety or sleep disorders. We controlled BP fluctuations by dividing the total daily levodopa and benserazide (Madopar) dose into smaller doses given more often, adding a sedative, and carrying out some simple nonmedical treatments for postprandial and orthostatic hypotension. At the same time, “dyskinesia” and “wearing-off” were also improved. BP fluctuations have a considerable influence on patients' quality of life and can even be life-threatening. The mechanism is complex, therefore a correct analysis of the underlying causes is needed to carry out comprehensive management. Adjustment of levodopa administration can not only stabilize BP well, but also can control PD motor complications.