Neuroanatomical substrates of visual hallucinations in patients with non-demented Parkinson's disease

J Neurol Neurosurg Psychiatry. 2012 Aug 29. [Epub ahead of print]

Shin S, Lee JE, Hong JY, Sunwoo MK, Sohn YH, Lee PH.

Source

Department of Neurology and Brain Research Institute, Yonsei University College of Medicine, Seoul, Korea.

Abstract

BACKGROUND:

Visual hallucinations (VH), which are common in patients with Parkinson's disease (PD), lead to increased disability and are a significant predictor of the development of dementia. However, the neuroanatomical basis for VH in non-demented PD patients remains controversial.

METHODS:

A total of 110 patients with PD were classified into PD with VH (n=46) and PD without VH (n=64) groups, depending on the presence of VH assessed by the caregiver-based structured interview of the Neuropsychiatric Inventory. We performed voxel-based morphometry (VBM) for grey matter (GM) volume and a region-of-interest-based volumetric analysis of the substantia innominata (SI) between two groups.

RESULTS:

The comprehensive neuropsychological assessment showed that PD patients with VH showed more severe cognitive deficits in delayed visual memory and frontal executive functions compared with those without VH. A VBM analysis revealed that PD patients with VH had significantly lower GM volume in the right orbitofrontal, left temporal and left thalamic areas compared with those without VH. The normalised SI volume was significantly reduced in PD patients with VH compared with those without VH (1.28±0.22 vs 1.41±0.25, p=0.005).

CONCLUSIONS:

The present study demonstrates that non-demented PD patients with VH exhibited a smaller volume in the frontal, temporal and thalamic areas as well as the SI, suggesting that PD hallucinators may have distinctive neuroanatomical bases relative to PD non-hallucinators.

Clinical features of dopamine agonist withdrawal syndrome in a movement disorders clinic

J Neurol Neurosurg Psychiatry. 2012 Aug 29. [Epub ahead of print]

Pondal M, Marras C, Miyasaki J, Moro E, Armstrong MJ, Strafella AP, Shah BB, Fox S, Prashanth LK, Phielipp N, Lang AE.

Source

The Morton and Gloria Shulman Movement Disorders Centre and the Edmond J. Safra Program in Parkinson's Disease, University Health Network and University of Toronto, Toronto, Ontario, Canada.

Abstract

BACKGROUND:

Recently, symptoms similar to addictive drug withdrawal have been reported in a structured longitudinal study of patients with idiopathic Parkinson's Disease (PD) withdrawing from dopamine agonists (DA): the dopamine agonist withdrawal syndrome (DAWS).

OBJECTIVES:

The objective of this study was to establish the frequency, predictors, and outcomes of DAWS in a movement disorders clinic.

METHODS:

We conducted a retrospective chart review of a sample of patients with a clinical diagnosis of PD treated with DA in whom withdrawal or attempted withdrawal of DA was carried out because of adverse effects, or for any other reason. Out of 487 PD patient charts reviewed, 84 were withdrawn from the agonists and were evaluable.

RESULTS:

Thirteen patients (15.5%) met criteria for DAWS (DAWS+) and 71 did not (DAWS-). DAWS developed upon withdrawal from pergolide, pramipexole and ropinirole, and did not respond to levodopa. DAWS outcomes included recovery in less than 6 months in 61%, in more than a year in 23%, and an inability to discontinue DA in 15% of patients. Development of impulse control disorders was the reason for DA withdrawal in all DAWS+, but only in 41% of DAWS- patients (p<0.0001). DAWS+ and DAWS- patients did not differ in other variables.

CONCLUSION:

DAWS is a disabling complication of DA use. Critical features of the syndrome are the strong link with impulse control disorders, possibly the independence of DA dosage and type, and the resistance to treatment, including levodopa. Further studies are required to characterise those at risk as well as to define an effective treatment.

Vitamin D and Parkinson's disease

J Neurosci Res. 2012 Aug 28. doi: 10.1002/jnr.23115. [Epub ahead of print]

Vinh Quôc Luong K, Thi Hoàng Nguyên L.

Source

Vietnamese American Medical Research Foundation, Westminster, California.

Abstract

Parkinson's disease (PD) is the second most common form of neurodegeneration among the elderly population. PD is clinically characterized by tremors, rigidity, slowness of movement, and postural imbalance. Interestingly, a significant association has been demonstrated between PD and low levels of vitamin D in the serum, and vitamin D supplement appears to have a beneficial clinical effect on PD. Genetic studies have provided the opportunity to determine which proteins link vitamin D to PD pathology, e.g., Nurr1 gene, toll-like receptor, gene related to lipid disorders, vascular endothelial factor, tyrosine hydroxylase, and angiogenin. Vitamin D also exerts its effects on cancer through nongenomic factors, e.g., bacillus Calmette-Guerin vaccination, interleukin-10, Wntβ-catenin signaling pathways, mitogen-activated protein kinase pathways, and the reduced form of the nicotinamide adenine dinucleotide phosphate. In conclusion, vitamin D might have a beneficial role in PD. Calcitriol is best used for PD because it is the active form of the vitamin D(3) metabolite and modulates inflammatory cytokine expression. Further investigation with calcitriol in PD is needed.

Selegiline prescriptions might be difficult to obtain until early October

I understand that some people are having difficulty getting 5mg tablets of Selegiline from their local pharmacy in the UK. It appears that there is a problem with manufacturing that is likely to be resolved in the coming weeks. Possible options in the interim include halving a 10mg Selegiline tablet, using the liquid form or the branded form of the drug. This should be discussed with your doctor or pharmacist if it affects you obtaining your repeat prescription.

Caffeine and risk of Parkinson's disease in a large cohort of men and women

Mov Disord. 2012 Aug 27. doi: 10.1002/mds.25076. [Epub ahead of print]

Palacios N, Gao X, McCullough ML, Schwarzschild MA, Shah R, Gapstur S, Ascherio A.

Source

Department of Nutrition, Harvard School of Public Health, Boston, Massachusetts, USA. 

Abstract

Caffeine consumption has been associated with a reduced risk of Parkinson's disease (PD). The association is strong and consistent in men, but uncertain in women, possibly because of an interaction with hormone replacement therapy (HRT). We sought to confirm these findings using data on PD incidence in the Cancer Prevention Study II Nutrition Cohort (CPS II-Nutrition), a large, prospective study of men and women. We conducted a prospective study of caffeine intake and risk of PD within the CPS II Nutrition Cohort. Intakes of coffee and other sources of caffeine were assessed at baseline. Incident cases of PD (n = 317; 197 men and 120 women) were confirmed by treating physicians and medical record review. Relative risks (RRs) were estimated using proportional hazards models, adjusting for age, smoking, and alcohol consumption. After adjustment for age, smoking, and alcohol intake, high caffeine consumption was associated with a reduced risk of PD. The RR comparing the 5th to the 1st quintile of caffeine intake was 0.43 (95% confidence interval [CI]: 0.26, 0.71; P trend = <0.002) in men, and 0.61 (95% CI: 0.34, 1.09; P trend = 0.05) in women. Among women, this association was stronger among never users of HRT (RR = 0.32) than among ever users (RR = 0.81; P interaction = 0.15). Consumption of decaffeinated coffee was not associated with PD risk. Findings from this large, prospective study of men and women are consistent with a protective effect of caffeine intake on PD incidence, with an attenuating influence of HRT in women.

Image from www.wikipedia.org

Frequency, prevalence, incidence and risk factors associated with visual hallucinations in a sample of patients with Parkinson's disease: a longitudinal 4-year study

Int J Geriatr Psychiatry. 2012 Aug 28. doi: 10.1002/gps.3869. [Epub ahead of print]

Gibson G, Mottram PG, Burn DJ, Hindle JV, Landau S, Samuel M, Hurt CS, Brown RG, Wilson KC.

Source

Institute of Health and Society, Newcastle University, Newcastle, UK. g.gibson@liverpool.ac.uk.

Abstract

OBJECTIVE:

To examine the prevalence, incidence and risk factors associated with visual hallucinations (VHs) amongst people suffering from Parkinson's disease (PD).

METHODS:

We recruited 513 patients with PD from movement disorder and PD clinics within three sites in the UK. Patients were interviewed using a series of standardised clinical rating scales at baseline, 12, 24 and 36 months. Data relating to VHs were collected using the North-East Visual Hallucinations Interview. Prevalence rates for VHs at each assessment were recorded. Associations were determined using multiple regression analysis.

RESULTS:

Cross-sectional prevalence rates for VHs at baseline, 12, 24 and 36 months indicated VHs in approximately 50% of patients. A cumulative frequency of 82.7% of cases at the end of the study period exhibited VHs. The incidence rate for VHs was 457 cases per 1000 population. Longer disease duration, greater impairment in activities of daily living and higher rates of anxiety were most commonly associated with VHs. No factors predictive of VHs could be ascertained.

CONCLUSIONS:

When examined longitudinally, VHs affect more patients than is commonly assumed in cross-sectional prevalence studies. Clinicians should routinely screen for VHs throughout the disease course. Disease duration, impairment in activities of daily living and anxiety presented as co-morbidities associated with VHs in PD, and therefore those presenting with VHs should be screened for anxiety disorder and vice versa.

Lysosome-dependent pathways as a unifying theme in Parkinson's disease.

Mov Disord. 2012 Aug 23. doi: 10.1002/mds.25136. [Epub ahead of print]

Tofaris GK.

Source

Nuffield Department of Clinical Neurosciences and Oxford Parkinson's Disease Center, University of Oxford, Oxford, United Kingdom. george.tofaris@ndcn.ox.ac.uk.

Abstract

Although the pathogenesis of Parkinson's disease (PD) is considered multifactorial, evidence from genetics and cell biology has implicated specific molecular pathways. This article summarizes evidence that suggests that the level of intracellular alpha-synuclein is critical for the onset of neurodegeneration with Lewy bodies and dependent, to a large extent, on lysosomal degradation. The function of other key proteins that emerged from genetics is discussed: Pink1 and Parkin regulate the degradation of damaged mitochondria by the lysosome (mitophagy). Glucocerebrosidase and ATP13A2 are important components of this degradative organelle. VPS35 and LRRK2 may regulate trafficking within lysosome-dependent pathways, such as autophagy and endosomal vesicle recycling. Clinically, diffuse alpha-synucleinopathy or dementia seems to correlate with mutations which interfere with the broader function of lysosomal pathways, whereas a predominantly motor syndrome and nigrostriatal degeneration is associated with specific defects in mitophagy. Based on these studies, it is proposed that a protein network involved in trafficking to, or degradation by, lysosomes could be sufficient to explain the phenotypic spectrum within PD in a unifying biochemical pathway.

A randomized trial of mesenchymal stem cells in multiple system atrophy

Ann Neurol. 2012 Jul;72(1):32-40. doi: 10.1002/ana.23612.
Lee PH, Lee JE, Kim HS, Song SK, Lee HS, Nam HS, Cheong JW, Jeong Y, Park HJ, Kim DJ, Nam CM, Lee JD, Kim HO, Sohn YH.

Source
Department of Neurology, Yonsei University College of Medicine, Seoul; Severance Biomedical Science Institute, Yonsei University, Seoul.
Abstract

OBJECTIVE:
Neuroprotective or regenerative strategies are invaluable in multiple system atrophy (MSA) due to its rapid progression with fatal prognosis. We evaluated the efficacy of autologous mesenchymal stem cells (MSC) in patients with MSA-cerebellar type (MSA-C).

METHODS:
Thirty-three patients with probable MSA-C and baseline unified MSA rating scale (UMSARS) scores ranging from 30 to 50 were randomly assigned to receive MSC (4 × 10(7) /injection) via intra-arterial and intravenous routes or placebo. The primary outcome was change in the total UMSARS scores from baseline throughout a 360-day follow-up period between groups. Secondary outcomes were changes in the UMSARS part II scores, cerebral glucose metabolism, gray matter density, and cognitive performance over a 360-day period.

RESULTS:
The mixed model analysis of neurological deficits revealed a significant interaction effect between treatment group and time, suggesting that the MSC group had a smaller increase in total and part II UMSARS scores compared with the placebo group (p = 0.047 and p = 0.008, respectively). Cerebral glucose metabolism and gray matter density at 360 days relative to the baseline were more extensively decreased in the cerebellum and the cerebral cortical areas, along with greater deterioration of frontal cognition in the placebo group compared with the MSC group. We found no serious adverse effects that were directly related to MSC treatment. However, intra-arterial infusion resulted in small ischemic lesions on magnetic resonance imaging.

INTERPRETATION:
MSC therapy could delay the progression of neurological deficits in patients with MSA-C, suggesting the potential of MSC therapy as a treatment candidate of MSA.

Parkinson's disease-like midbrain hyperechogenicity is frequent in amyotrophic lateral sclerosis

J Neurol. 2012 Aug 26. [Epub ahead of print]

Fathinia P, Hermann A, Reuner U, Kassubek J, Storch A, Ludolph AC.

Source

Department of Neurology, University of Ulm, Oberer Eselsberg 45, 89081, Ulm, Germany.

Abstract

Clinical and neuroimaging data suggest impairment of the nigrostriatal system in amyotrophic lateral sclerosis (ALS). We thus hypothesized whether Parkinson's disease (PD)-like midbrain sonography findings are also present in ALS. Eighty-six patients with the diagnosis of possible or definite ALS according to revised El Escorial criteria were examined by transcranial B-mode sonography compared to 76 age- and gender-matched controls and 33 PD patients. Hyperechogenic areas of the midbrain representing the substantia nigra were measured planimetrically using standard protocols. In subjects with sufficient temporal acoustic bone windows, mean midbrain hyperechogenic areas were significantly higher in ALS (0.251 ± 0.104 cm(2)) and PD patients (0.286 ± 0.078 cm(2)) compared to controls (0.091 ± 0.054 cm(2)) with no significant difference between ALS and PD patients (one-way ANOVA: F value = 94.3; P < 0.0001). Sixty-seven percent (95 % CI 57-78 %) of ALS patients and 84 % (95 % CI 71-97 %) of PD patients displayed abnormal midbrain hyperechogenic areas (P = 0.383 for group comparison, χ(2) test). No correlations of hyperechogenic area sizes in ALS patients were found in regard to age, gender, ALS subtype (bulbar versus spinal form) or ALS-FRS-R score. In summary, we observed hyperechogenicity of the substantia nigra in patients with sporadic ALS with a frequency similar to that in PD and higher than in all other movement disorders. These findings are important for the diagnosis and differential diagnosis of PD and ALS alike.

Recommendations to standardize preanalytical confounding factors in Alzheimer's and Parkinson's disease cerebrospinal fluid biomarkers: an update

Biomark Med. 2012 Aug;6(4):419-30.

Del Campo M, Mollenhauer B, Bertolotto A, Engelborghs S, Hampel H, Simonsen AH, Kapaki E, Kruse N, Le Bastard N, Lehmann S, Molinuevo JL, Parnetti L, Perret-Liaudet A, Sáez-Valero J, Saka E, Urbani A, Vanmechelen E, Verbeek M, Visser PJ, Teunissen C.

Abstract

Early diagnosis of neurodegenerative disorders such as Alzheimer's (AD) or Parkinson's disease (PD) is needed to slow down or halt the disease at the earliest stage. Cerebrospinal fluid (CSF) biomarkers can be a good tool for early diagnosis. However, their use in clinical practice is challenging due to the high variability found between centers in the concentrations of both AD CSF biomarkers (Aβ42, total tau and phosphorylated tau) and PD CSF biomarker (α-synuclein). Such a variability has been partially attributed to different preanalytical procedures between laboratories, thus highlighting the need to establish standardized operating procedures. Here, we merge two previous consensus guidelines for preanalytical confounding factors in order to achieve one exhaustive guideline updated with new evidence for Aβ42, total tau and phosphorylated tau, and α-synuclein. The proposed standardized operating procedures are applicable not only to novel CSF biomarkers in AD and PD, but also to biomarkers for other neurodegenerative disorders.

The effect of pramipexole therapy on balance disorder and fall risk in Parkinson's disease at early stage: clinical and posturographic assessment

ISRN Neurol. 2012;2012:320607. Epub 2012 Aug 5.

Güler S, Bir LS, Akdag B, Ardıc F.

Source

Department of Neurology, Faculty of Medicine, Trakya University, 22030 Edirne, Turkey.

Abstract

The aim of this study was to determine balance problems and severity and ratio of postural instability of newly diagnosed, early stage Parkinson's patients who did not receive any antiparkinson treatment before, to evaluate fall risk clinically and posturographically and to examine the effects of pramipexole on these signs and symptoms. Detailed posturographic assessments which involved central vestibular, visual, peripheric vestibular somatosensory field tests were applied to both patient and control subjects and fall risk was determined. There was not statistically significant difference between patients and control subjects before and after drug therapy in the assesment of fall risk in posturography and there was not any improvement with drug usage in the patient group. However, in the analysis of subsystems separately, only the involvement in central vestibular field was more severe and could appear at all positions in Parkinson's patients comparing with the control group, and pramipexole was partially effective in improving this disorder. Central vestibular field is the subsystem that should be examined with first priority. Posturography is relatively reliable in defining fall risk and postural instability ratio in Parkinson's disease. But it should be considered that clinical assessment tools can be more sensitive in the evaluation of balance and postural disorders and in the follow-up of the response to drug therapy.

Obesity phenotypes in midlife and cognition in early old age: The Whitehall II cohort study

Archana Singh-Manoux, PhD, Sébastien Czernichow, MD, PhD, Alexis Elbaz, MD, PhD, Aline Dugravot, MSc, Séverine Sabia, PhD, Gareth Hagger-Johnson, PhD, Sara Kaffashian, MSc, Marie Zins, MD, PhD, Eric J. Brunner, PhD, Hermann Nabi, PhD and Mika Kivimäki, PhD

ABSTRACT

Objective: To examine the association of body mass index (BMI) and metabolic status with cognitive function and decline.

Methods: A total of 6,401 adults (71.2% men), aged 39–63 years in 1991–1993, provided data on BMI (normal weight 18.5–24.9 kg/m², overweight 25–29.9 kg/m²; and obese ≥30 kg/m²) and metabolic status (abnormality defined as 2 or more of 1) triglycerides ≥1.69 mmol/L or lipid-lowering drugs, 2) systolic blood pressure ≥130 mm Hg, diastolic blood pressure ≥85 mm Hg, or antihypertensive drugs, 3) glucose ≥5.6 mmol/L or medications for diabetes, and 4) high-density lipoprotein cholesterol <1.04 mmol/L for men and <1.29 mmol/L for women). Four cognitive tests (memory, reasoning, semantic, and phonemic fluency) were administered in 1997–1999, 2002–2004, and 2007–2009, standardized to z scores, and averaged to yield a global score.

Results: Of the participants, 31.0% had metabolic abnormalities, 52.7% were normal weight, 38.2% were overweight, and 9.1% were obese. Among the obese, the global cognitive score at baseline (p = 0.82) and decline (p = 0.19) over 10 years was similar in the metabolically normal and abnormal groups. In the metabolically normal group, the 10-year decline in the global cognitive score was similar (p for trend = 0.36) in the normal weight (−0.40; 95% confidence interval [CI] −0.42 to −0.38), overweight (−0.42; 95% CI −0.45 to −0.39), and obese (−0.42; 95% CI −0.50 to −0.34) groups. However, in the metabolically abnormal group, the decline on the global score was faster among obese (−0.49; 95% CI −0.55 to −0.42) than among normal weight individuals (−0.42; 95% CI −0.50 to −0.34), (p = 0.03).

Conclusions: In these analyses the fastest cognitive decline was observed in those with both obesity and metabolic abnormality.

Effect of bilateral deep brain stimulation of the subthalamic nucleus on freezing of gait in Parkinson's disease

J Int Med Res. 2012;40(3):1108-13.

Niu L, Ji LY, Li JM, Zhao DS, Huang G, Liu WP, Qu Y, Ma LT, Ji XT.

Source

Department of Neurosurgery, Xijing Hospital, The Fourth Military Medical University, Xi'an, China; Department of Neurosurgery, Wuhan General Hospital, Guangzhou Command of The People's Liberation Army, Wuhan, China.

Abstract

OBJECTIVE:

A prospective cohort study to evaluate the efficacy of bilateral subthalamic nucleus deep brain stimulation (STN-DBS) on freezing of gait (FOG) in patients with advanced Parkinson's disease.

METHODS:

Patients (n = 10) with advanced Parkinson's disease were surgically implanted with microelectrodes to facilitate STN-DBS. Evaluations of FOG, motor function, activities of daily living and neuropsychological function were carried out in on-medication and off-medication states (with and without levodopa treatment), before surgery and at 6 and 12 months postoperatively.

RESULTS:

STN-DBS was associated with significant improvement in FOG score and neuropsychological function at both 6 and 12 months postoperatively, compared with preoperatively. Significant postoperative improvements were also observed in motor function and activities of daily living. Daily levodopa dosage was significantly lower at both 6 and 12 months postoperatively.

CONCLUSIONS:

STN-DBS improved FOG in patients with advanced Parkinson's disease. The significant reduction in levodopa dosage and improvement in neuropsychological function may be the reason for the therapeutic effect seen with STN-DBS.

Genome wide assessment of young onset Parkinson's disease from Finland

PLoS One. 2012;7(7):e41859. Epub 2012 Jul 24.

Hernandez DG, Nalls MA, Ylikotila P, Keller M, Hardy JA, Majamaa K, Singleton AB.

Source

Laboratory of Neurogenetics, National Institute on Aging, National Institutes of Health, Bethesda, Maryland, United States of America.

Abstract

In the current study we undertook a series of experiments to test the hypothesis that a monogenic cause of disease may be detectable within a cohort of Finnish young onset Parkinson's disease patients. In the first instance we performed standard genome wide association analyses, and subsequent risk profile analysis. In addition we performed a series of analyses that involved testing measures of global relatedness within the cases compared to controls, searching for excess homozygosity in the cases, and examining the cases for signs of excess local genomic relatedness using a sliding window approach. This work suggested that the previously identified common, low risk alleles, and the risk models associated with these alleles, were generalizable to the Finnish Parkinson's disease population. However, we found no evidence that would suggest a single common high penetrance mutation exists in this cohort of young onset patients.

Parkinson's disease and parkinsonism: neuropathology

Cold Spring Harb Perspect Med. 2012 Aug 1;2(8). pii: a009258. doi: 10.1101/cshperspect.a009258.

Dickson DW.

Source

Department of Neuroscience, Mayo Clinic, Jacksonville, Florida 32224.

Abstract

Parkinsonism, the clinical term for a disorder with prominent bradykinesia and variable associated extrapyramidal signs and symptoms, is accompanied by degeneration of the nigrostriatal dopaminergic system, with neuronal loss and reactive gliosis in the substantia nigra found at autopsy. Parkinsonism is pathologically heterogeneous, with the most common pathologic substrates related to abnormalities in the presynaptic protein α-synuclein or the microtubule binding protein tau. In idiopathic Parkinson's disease (PD), α-synuclein accumulates in neuronal perikarya (Lewy bodies) and neuronal processes (Lewy neurites). The disease process is multifocal and involves select central nervous system neurons and peripheral autonomic nervous system neurons. The particular set of neurons affected determines nonmotor clinical presentations. Multiple system atrophy (MSA) is the other major α-synucleinopathy. It is also associated with autonomic dysfunction and in some cases with cerebellar signs. The hallmark histopathologic feature of MSA is accumulation of α-synuclein within glial cytoplasmic inclusions (GCI). The most common of the Parkinsonian tauopathies is progressive supranuclear palsy (PSP), which is clinically associated with severe postural instability leading to early falls. The tau pathology of PSP also affects both neurons and glia. Given the population frequency of PD, α-synuclein pathology similar to that in PD, but not accompanied by neuronal loss, is relatively common (10% of people over 65 years of age) in neurologically normal individuals, leading to proposed staging schemes for PD progression. Although MSA-like and PSP-like pathology can be detected in neurologically normal individuals, such cases are too infrequent to permit assessment of patterns of disease progression.

A Lewy body 

Source: wikepedia.org

Clinical features and 123I-FP-CIT SPECT imaging in vascular parkinsonism and Parkinson's disease

J Neurol Neurosurg Psychiatry. 2012 Aug 20. [Epub ahead of print]

Benítez-Rivero S, Marín-Oyaga VA, García-Solís D, Huertas-Fernández I, García-Gómez FJ, Jesús S, Cáceres MT, Carrillo F, Ortiz AM, Carballo M, Mir P.

Source

Unidad de Trastornos del Movimiento, Servicio de Neurología y Neurofisiología Clínica, Instituto de Biomedicina de Sevilla (IBiS), Hospital Universitario Virgen del Rocío/CSIC/Universidad de Sevilla, Seville, Spain.

Abstract

Objectives- To analyse the differences in the clinical features and characteristics of (123)I-labelled 2β-carbomethoxy-3β-(4-iodophenyl)-N-(3-fluoropropyl) nortropane ((123)I-FP-CIT) single photon emission CT (SPECT) imaging among patients with vascular parkinsonism (VP) and Parkinson's disease (PD).

Methods- We performed a case-control study to compare clinical features and qualitative and semi-quantitative analyses of (123)I-FP-CIT SPECT images between 106 patients with VP and 280 patients with PD. A case series study was used to search for clinical features related to SPECT or neuroimaging findings among patients with VP.

Results- Patients with VP had a higher age at symptom onset and lower disease duration than patients with PD. The most frequent symptom at onset was gait disorder in VP and tremor in PD. Gait disorder, postural instability and falls were more frequent in VP. Rest and mixed tremor were more prevalent in PD. Of the patients who received levodopa treatment in the VP group, only about half had a good response. Qualitatively (123)I-FP-CIT SPECT images were normal in 32.5% of patients with VP and abnormal in all patients with PD. The use of different visual score patterns showed higher ability to differentiate VP from PD. Semi-quantitative analysis showed significantly higher uptake in the striatum, caudate and putamen in VP. The asymmetry index was higher in patients with PD. Among patients with VP, falls were the only clinical feature that demonstrated a correlation with the SPECT visual pattern.

Conclusion- Our data contribute to the confirmation that VP and PD are two different clinical entities. Neurological signs, response to treatment and qualitative and semi-quantitative (123)I-FP-CIT SPECT analyses may help to make the diagnosis.

Prevalence of non motor features in a cohort of Parkinson's disease patients

Clin Neurol Neurosurg. 2012 Aug 16. [Epub ahead of print]

Khedr EM, El Fetoh NA, Khalifa H, Ahmed MA, El Beh KM.

Source

Department of Neuropsychiatry, Assiut University Hospital, Assiut, Egypt; Department of Psychiatry, Assiut University Hospital, Assiut, Egypt.

Abstract

BACKGROUND:

There is a lack of awareness among physicians of the considerable disability caused by non-motor symptoms (NMS) in PD. The aim of this work is to estimate the prevalence of NMS in a series of patients with Parkinson's disease (PD).

MATERIALS AND METHODS:

We studied 112 patients with Parkinson's disease. Motor symptoms were scored on the Unified Parkinson's Disease Rating Scale (UPDRS) part III and the Hoehn and Yahr (HY) Scale. Other symptoms were quantified with the Non-Motor Symptom Questionnaire and Scale (NMSQuest and NMSS) as well as Minimental State Examination (MNSE).

RESULTS:

Analysis of the data from the NMSS showed that mood/cognition was the most commonly affected domain (prevalence rate=87.5%), followed by sleep disturbance/fatigue second (78.6%). However, all other non-motor symptoms scored highly: gastrointestinal and urinary (76.8% for both), sexual dysfunction (73%), cardiovascular (70.5%) with significantly higher percentage in predominantly akinetic/rigid patients. Perceptual problems/hallucinations (9.9%) were infrequent in this population. Dementia was recorded in 22.3% of patients, most of them having a mild degree of dementia. UPDRS scores were correlated with total scores in both NMSQuest and NMSS.

CONCLUSIONS:

Mood/cognition, sleep disorders, GIT, and sexual disorders were common non motor manifestations in this population of PD patients.

Prevalence of oropharyngeal dysphagia in Parkinson's disease: a meta-analysis

Parkinsonism and Related Disorders

Volume 18, Issue 4, May 2012, Pages 311-315

Kalf, J.G.^ab , de Swart, B.J.M.^a, Bloem, B.R.^b, Munneke, M.^c  

^a  Radboud University Nijmegen Medical Centre, Nijmegen Centre for Evidence Based Practice, Department of Rehabilitation, Netherlands
^b  Radboud University Nijmegen Medical Centre, Donders Institute for Brain, Cognition and Behaviour, Centre for Neuroscience, Netherlands
^c  Radboud University Nijmegen Medical Centre, Nijmegen Centre for Evidence Based Practice, IQ Healthcare, Scientific Institute for Health Care, Netherlands

Abstract

Dysphagia is a potentially harmful feature, also in Parkinson's disease (PD). As published prevalence rates vary widely, we aimed to estimate the prevalence of oropharyngeal dysphagia in PD in a meta-analysis. We conducted a systematic literature search in February 2011 and two independent reviewers selected the papers. We computed the estimates of the pooled prevalence weighted by sample size. Twelve studies were suitable for calculating prevalence rates. Ten studies provided an estimate based on subjective outcomes, which proved statistically heterogeneous (p < 0.001), with a pooled prevalence estimate with random effect analysis of 35% (95% CI 28-41). Four studies provided an estimate based on objective measurements, which were statistically homogeneous (p = 0.23), with a pooled prevalence estimate of 82% (95% CI 77-87). In controls the pooled subjective prevalence was 9% (95% CI 2-17), while the pooled objective prevalence was 23% (95% CI 13-32). The pooled relative risk was 3.2 for both subjective outcomes (95% CI 2.32-4.41) and objective outcomes (95% CI 2.08-4.98). Clinical heterogeneity between studies was chiefly explained by differences in disease severity. Subjective dysphagia occurs in one third of community-dwelling PD patients. Objectively measured dysphagia rates were much higher, with 4 out of 5 patients being affected. This suggests that dysphagia is common in PD, but patients do not always report swallowing difficulties unless asked. This underreporting calls for a proactive clinical approach to dysphagia, particularly in light of the serious clinical consequences.

Comparison of speech and language therapy techniques for speech problems in Parkinson's disease

Cochrane Database Syst Rev. 2012 Aug 15;8:CD002814.

Herd CP, Tomlinson CL, Deane KH, Brady MC, Smith CH, Sackley CM, Clarke CE.

Source

School of Clinical and Experimental Medicine, College of Medical and Dental Sciences, University of Birmingham, Edgbaston, Birmingham, UK, B15 2TT.

Abstract

BACKGROUND:

Patients with Parkinson's disease commonly suffer from speech and voice difficulties such as impaired articulation and reduced loudness. Speech and language therapy (SLT) aims to improve the intelligibility of speech with behavioural treatment techniques or instrumental aids.

OBJECTIVES:

To compare the efficacy and effectiveness of novel SLT techniques versus a standard SLT approach to treat Parkinsonian speech problems.

SEARCH METHODS:

We identified relevant, published prior to 11(th) April 2011, by electronic searches of numerous literature databases including CENTRAL, MEDLINE and CINAHL, as well as handsearching relevant conference abstracts and examining reference lists in identified studies and other reviews.

SELECTION CRITERIA:

Only randomised controlled trials (RCT) of one type of speech and language therapy versus another were included.

DATA COLLECTION AND ANALYSIS:

Two review authors independently extracted data and resolved differences by discussion.

MAIN RESULTS:

Six trials involving 159 patients satisfied the inclusion criteria. Data could not be analysed from one trial due to changes in patient numbers and from a second because the data provided were not in a usable format. All trials reported intelligibility measures but a statistically significant result was only reported for the diagnostic rhyme test used in the study of Lee Silverman Voice Treatment -LOUD (LSVT-LOUD) versus a modified version of this therapy (LSVT-ARTIC). In this case a difference of 12.5 points (95% confidence interval (CI) -22.2 to -2.8; P = 0.01) between the mean changes in favour of the LSVT-LOUD group was reported for a speech sample overlaid with Babble noise; this difference was not reproduced for the two additional noise conditions under which the speech samples were assessed. LSVT-LOUD also outperformed LSVT-ARTIC and Respiration therapy (RT) in improving loudness, with a difference in reading a sample text of 5.0 dB (95%CI -8.3 to -1.7; P = 0.003) and 5.5 dB (95% CI 3.4 to 7.7; P < 0.00001) respectively, and a difference in monologue speech of 2.9 dB (95% CI 0.6 to 5.2; P = 0.01) versus RT.

AUTHORS' CONCLUSIONS:

Considering the small patient numbers in these trials, there is insufficient evidence to support or refute the efficacy of any form of SLT over another to treat speech problems in patients with Parkinson's disease.

Effect of Nintendo Wii™-based motor and cognitive training on activities of daily living in patients with Parkinson's disease: A randomised clinical trial

Physiotherapy. 2012 Sep;98(3):196-204. Epub 2012 Jul 25.

Pompeu JE, Mendes FA, Silva KG, Lobo AM, Oliveira Tde P, Zomignani AP, Piemonte ME.

Source

São Paulo University, São Paulo, Brazil.

Abstract

OBJECTIVES:

To investigate the effect of Nintendo Wii™-based motor cognitive training versus balance exercise therapy on activities of daily living in patients with Parkinson's disease.

DESIGN:

Parallel, prospective, single-blind, randomised clinical trial.

SETTING:

Brazilian Parkinson Association.

PARTICIPANTS:

Thirty-two patients with Parkinson's disease (Hoehn and Yahr stages 1 and 2).

INTERVENTIONS:

Fourteen training sessions consisting of 30 minutes of stretching, strengthening and axial mobility exercises, plus 30 minutes of balance training. The control group performed balance exercises without feedback or cognitive stimulation, and the experimental group performed 10 Wii Fit™ games.

MAIN OUTCOME MEASURE:

Section II of the Unified Parkinson's Disease Rating Scale (UPDRS-II). RANDOMISATION: Participants were randomised into a control group (n=16) and an experimental group (n=16) through blinded drawing of names.

STATISTICAL ANALYSIS:

Repeated-measures analysis of variance (RM-ANOVA).

RESULTS:

Both groups showed improvement in the UPDRS-II with assessment effect (RM-ANOVA P<0.001, observed power=0.999). There was no difference between the control group and the experimental group before training {8.9 [standard deviation (SD) 2.9] vs 10.1 (SD 3.8)}, after training [7.6 (SD 2.9) vs 8.1 (SD 3.5)] or 60 days after training [8.1 (SD 3.2) vs 8.3 (SD 3.6)]. The mean difference of the whole group between before training and after training was -0.9 (SD 2.3, 95% confidence interval -1.7 to -0.6).

CONCLUSION:

Patients with Parkinson's disease showed improved performance in activities of daily living after 14 sessions of balance training, with no additional advantages associated with the Wii-based motor and cognitive training. Registered on http://www.clinicaltrials.gov (identifier: NCT01580787).

Image from http://www.procprblog.com/

Defective Autophagy in Parkinson's Disease: Role of Oxidative Stress

Mol Neurobiol. 2012 Aug 17. [Epub ahead of print]

Janda E, Isidoro C, Carresi C, Mollace V.

Source

Department of Health Sciences, University "Magna Graecia", Edificio Bioscienze, viale Europa, Campus Salvatore Venuta, Germaneto, 88100, Catanzaro, Italy, janda@unicz.it.

Abstract

Parkinson's disease (PD) is a paradigmatic example of neurodegenerative disorder with a critical role of oxidative stress in its etiopathogenesis. Genetic susceptibility factors of PD, such as mutations in Parkin, PTEN-induced kinase 1, and DJ-1 as well as the exposure to pesticides and heavy metals, both contribute to altered redox balance and degeneration of dopaminergic neurons in the substantia nigra. Dysregulation of autophagy, a lysosomal-driven process of self degradation of cellular organelles and protein aggregates, is also implicated in PD and PD-related mutations, and environmental toxins deregulate autophagy. However, experimental evidence suggests a complex and ambiguous role of autophagy in PD since either impaired or abnormally upregulated autophagic flux has been shown to cause neuronal loss. Finally, it is generally believed that oxidative stress is a strong proautophagic stimulus. However, some evidence coming from neurobiology as well as from other fields indicate an inhibitory role of reactive oxygen species and reactive nitrogen species on the autophagic machinery. This review examines the scientific evidence supporting different concepts on how autophagy is dysregulated in PD and attempts to reconcile apparently contradictory views on the role of oxidative stress in autophagy regulation. The complex relationship between autophagy and oxidative stress is also considered in the context of the ongoing search for a novel PD therapy.

Interocular Asymmetry of Foveal Thickness in Parkinson Disease

J Ophthalmol. 2012;2012:728457. Epub 2012 Aug 1.

Shrier EM, Adam CR, Spund B, Glazman S, Bodis-Wollner I.

Source

Department of Ophthalmology, SUNY Downstate Medical Center, State University of New York, 450 Clarkson Avenue, Brooklyn, NY 11203, USA.

Abstract

Purpose. To quantify interocular asymmetry (IA) of foveal thickness in Parkinson disease (PD) versus that of controls. Design. Prospective case-control series. Methods. In vivo assessment of foveal thickness of 46 eyes of 23 PD patients and 36 eyes of 18 control subjects was studied using spectral domain optical coherence tomography (SD-OCT). Inner versus outer layer retinal segmentation and macular volumes were quantified using the manufacturer's software, while foveal thickness was measured using the raw data from each eye in a grid covering a 6 by 6 mm area centered on the foveola in 0.25 mm steps. Thickness data were entered into MATLAB software. Results. Macular volumes differed significantly at the largest (Zone 3) diameter centered on the foveola (ETDRS protocol). By segmenting inner from outer layers, we found that the IA in PD is mostly due to changes on the slope of the foveal pit at the radial distances of 0.5 and 0.75 mm (1.5 mm and 1 mm diameter). Conclusions. About half of the PD patients had IA of the slope of the foveal pit. IA is a potentially useful marker of PD and is expected to be comparable across different SD-OCT equipment. Data of larger groups may be developed in future multicenter studies.

Parkinson's disease among American Indians and Alaska natives: A nationwide prevalence study

Mov Disord. 2012 Aug 14. doi: 10.1002/mds.25153. [Epub ahead of print]

Gordon PH, Mehal JM, Holman RC, Rowland AS, Cheek JE.

Source

Indian Health Service, U.S. Department of Health and Human Services, Northern Navajo Medical Center, Shiprock, New Mexico, USA. paul.gordon@ihs.gov.

Abstract

BACKGROUND:

The objective of this study was to determine the prevalence of Parkinson's disease (PD) among American Indian and Alaska Native (AI/AN) people.

METHODS:

We analyzed records for AI/AN people between 2002 and 2009 using inpatient and outpatient visit data from the Indian Health Service. Crude and age-adjusted prevalence, using the 2000 projected US population as the standard, was determined overall and by age group, sex, period, and region.

RESULTS:

An estimated 2613 AI/AN people carried the diagnosis of PD (crude prevalence, 143.8/100,000). Prevalence increased with age through 84 years. The age-adjusted rate was 355.7 and was higher among men than women (P < .0001). Rates differed by region (P < .0001).

CONCLUSIONS:

Parkinson's disease is prevalent among AI/AN people. The prevalence increases with age, varies by geographic region, and is higher among men than women. Community-based studies are needed to define incidence, examine risk factors, and determine reasons for sex and regional differences in PD among AI/AN people.

Fascinating paper estimating the magnitude of the role the genetics still has to play in PD

Hum Mol Genet. 2012 Aug 13. [Epub ahead of print]

Using Genome-wide Complex Trait Analysis to quantify 'missing heritability' in Parkinson's disease.

Keller MF, Saad M, Bras JM, Bettella F, Nicolaou N, Simón-Sánchez J, Mittag F, Buechel F, Sharma M, Gibbs JR, Schulte C, Moskvina V, Durr A, Holmans P, Kilarski LL, Guerreiro R, Hernandez D, Brice A, Ylikotila P, Stefánsson H, Majamaa K, Morris HR, Williams N, Gasser T, Heutink P, Wood N, Hardy J, Martinez M, Singleton AB, Nalls MA; for the International Parkinson’s Disease Genomics Consortium (IPDGC) and The Wellcome Trust Case Control Consortium 2 (WTCCC2).

Source

Laboratory of Neurogenetics, National Institute on Aging, National Institutes of Health, Bethesda, Maryland, United States of America.

Abstract

Genome-wide association studies (GWAS) have been successful at identifying single nucleotide polymorphisms (SNPs) highly associated with common traits, however a great deal of the heritable variation associated with common traits remains unaccounted for within the genome. Genome-wide Complex Trait Analysis (GCTA) is a statistical method that applies a linear mixed model to estimate phenotypic variance of complex traits explained by genome-wide SNPs, including those not associated with the trait in a GWAS. We applied GCTA to 8 cohorts containing 7,096 case and 19,455 control individuals of European ancestry in order to examine the missing heritability present in Parkinson's disease (PD). We meta-analyzed our initial results to produce robust heritability estimates for PD types across cohorts. Our results identify 27% (95% CI [17%, 38%], p = 8.08E-08) phenotypic variance associated with all types of PD, 15% (95% CI [-0.2%, 33%], p = 0.09) phenotypic variance associated with early onset PD, and 31% (95% CI [17%, 44%], p = 1.34E-05) phenotypic variance associated with late onset PD. This is a substantial increase from the genetic variance identified by top GWAS hits alone (between 3-5%) and indicates there are substantially more risk loci to be identified. Our results suggest that while GWAS is a useful tool in identifying the most common variants associated with complex disease, a great deal of common variants of small effect remain to be discovered.

The mechanism of γ-Secretase dysfunction in familial Alzheimer disease

EMBO J. 2012 Apr 13;31(10):2261-74. doi: 10.1038/emboj.2012.79.

Chávez-Gutiérrez L, Bammens L, Benilova I, Vandersteen A, Benurwar M, Borgers M, Lismont S, Zhou L, Van Cleynenbreugel S, Esselmann H, Wiltfang J, Serneels L, Karran E, Gijsen H, Schymkowitz J, Rousseau F, Broersen K, De Strooper B.

Source

VIB Center for the Biology of Disease, Leuven, Belgium.

Abstract

The mechanisms by which mutations in the presenilins (PSEN) or the amyloid precursor protein (APP) genes cause familial Alzheimer disease (FAD) are controversial. FAD mutations increase the release of amyloid β (Aβ)42 relative to Aβ40 by an unknown, possibly gain-of-toxic-function, mechanism. However, many PSEN mutations paradoxically impair γ-secretase and 'loss-of-function' mechanisms have also been postulated. Here, we use kinetic studies to demonstrate that FAD mutations affect Aβ generation via three different mechanisms, resulting in qualitative changes in the Aβ profiles, which are not limited to Aβ42. Loss of ɛ-cleavage function is not generally observed among FAD mutants. On the other hand, γ-secretase inhibitors used in the clinic appear to block the initial ɛ-cleavage step, but unexpectedly affect more selectively Notch than APP processing, while modulators act as activators of the carboxypeptidase-like (γ) activity. Overall, we provide a coherent explanation for the effect of different FAD mutations, demonstrating the importance of qualitative rather than quantitative changes in the Aβ products, and suggest fundamental improvements for current drug development efforts.

Association between Parkinson's disease and the HLA-DRB1 locus

Mov Disord. 2012 Aug;27(9):1104-10. doi: 10.1002/mds.25035. Epub 2012 Jul 13.

Ahmed I, Tamouza R, Delord M, Krishnamoorthy R, Tzourio C, Mulot C, Nacfer M, Lambert JC, Beaune P, Laurent-Puig P, Loriot MA, Charron D, Elbaz A.

Source

INSERM, U708, Neuroepidemiology, Paris, France; UPMC Univ Paris 06, UMR_S708, Neuroepidemiology, Paris, France. ismail.ahmed@inserm.fr.

Abstract

Two genome-wide association studies (GWASs) recently highlighted the HLA-DRA and HLA-DRB5 genes as associated with Parkinson disease (PD). However, because HLA-DRA displays a low level of polymorphisms and HLA-DRB5 is only present in approximately 20% of the population, these findings are difficult to interpret. Our aims were: (1) to replicate and investigate in greater detail the association between PD and the HLA-DR region; (2) to identify PD-associated HLA alleles; and (3) to perform a meta-analysis of our top finding. As part of 2 French population-based case-control studies of PD including highly ethnically homogeneous participants, we investigated the association between PD and 51 Single-nucleotide polymorphisms (SNPs) in the HLA-DR region. HLA-DRB1 alleles were imputed using the HLA(*) IMP software. HLA typing was performed in a subsample of the participants. We performed a meta-analysis of our top finding based on 4 GWAS data sets. Among 499 cases and 1123 controls, after correction for multiple testing, we found an association with rs660895 (OR/minor allele, 0.70; 95% CI, 0.57-0.87) within the HLA-DRB1 gene, which encodes the most polymorphic HLA-DR chain (DRβ). A meta-analysis (7996 cases, 36455 controls) confirmed this association (OR, 0.86; 95% CI, 0.82-0.91; P < .0001). SNP-based imputation of HLA alleles showed an inverse association between PD and the HLA-DRB1(*) 04 allele. We replicated an association between PD and the HLA-DR region and provided further insight into the loci and alleles involved. The highly polymorphic HLA-DRB1 locus contains rs660895, which represents a more legitimate candidate than previous ones. Our finding is in agreement with the hypothesis of an immune component in PD pathophysiology.

Sleep problems in Parkinson's disease: a community-based study in Norway

BMC Neurol. 2012 Aug 10;12(1):71. [Epub ahead of print]

Svensson E, Beiske AG, Loge JH, Beiske KK, Sivertsen B.

Abstract

BACKGROUND:

The purpose of this study was to examine the prevalence of sleep problems in a community-based sample of patients with Parkinson's disease (PD) in Norway, and their associated factors.

METHODS:

176 consecutive PD outpatients (41% females) were included in a study of non-motor symptoms, including sleep problems. All participants responded to the Parkinson's Disease Sleep Scale (PDSS), where an overall score below 82 or a score below 5 on a sub-item indicate possible sleep problem. Factors associated with sleep were also investigated, with special emphasis on severity of PD, fatigue, mental health and restless legs syndrome (RLS).

RESULTS:

The mean age was 68.5 years (range 35--90); the mean Hoehn and Yahr stage was 2.11 (SD 0.86), and the mean UPDRS part III was 22.3 (SD 11.7). Sleep problems were common among PD patients. While only 17% of the sample had an overall score below 82 on the PDSS, 70% of the patients had a score below 5 on one item. There was no significant association between PD severity and any of the sleep items in the PDSS; whereas fatigue, mental health problems, and RLS were associated with PDSS score.

CONCLUSIONS:

The current findings call for increased awareness of sleep problems in PD patients, especially focusing on the association with mental health problems, fatigue and RLS.

Self reported adherence to a home-based exercise programme among people with Parkinson's disease

Parkinsonism Relat Disord. 2012 Aug 6. [Epub ahead of print]

Pickering RM, Fitton C, Ballinger C, Fazakarley L, Ashburn A.

Source

Senior Lecturer in Medical Statistics, Public Health Sciences and Medical Statistics, University of Southampton, UK.

Abstract

BACKGROUND:

There is an extensive literature addressing compliance with medication, techniques to measure, and ways to improve it. In comparison the literature concerning adherence to exercise programmes agreed with a physiotherapist is limited.

OBJECTIVE:

We estimate the percentage of exercise repetitions completed of those agreed with a physiotherapist in the context of a six week personalized exercise programme to reduce falling in people with Parkinson's disease, and examine patient characteristics that predict adherence.

METHODS:

Secondary analysis of data collected during a randomized controlled trial. Participants allocated to receive the exercise programme self-reported the number of repetitions of prescribed strengthening, range of movement and balance exercises they had completed in daily dairies. Indoor or outdoor walking was also prescribed but in terms of target distances or lengths of time, and was not included in our analysis.

RESULTS:

On average the 70 participants allocated to the exercise programme reported completing 79% (95% confidence interval 73%-86%) of the prescribed number of repetitions of their exercises. The percentage of exercises completed varied depending on the specific exercise prescribed, and on participant characteristics: those who were older, in poorer health and with anxiety, depression, or mental heath problems reported lower adherence to exercise.

CONCLUSION:

Several of the factors we found to reduce adherence to exercise have been shown by others to reduce compliance with antiparkinsonian medication, but we found adherence decreased with age in contrast to the pattern of better compliance with medication amongst older people with Parkinson's disease reported previously.

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Does structural neuroimaging reveal a disturbance of iron metabolism in Parkinson's disease? Implications from MRI and TCS studies

J Neural Transm. 2012 Aug 9. [Epub ahead of print]

Gröger A, Berg D.

Source

Department of Neurodegeneration, Hertie Institute of Clinical Brain Research, and German Center of Neurodegenerative Diseases (DZNE), University of Tübingen, Hoppe-Seyler-Strasse 3, 72076, Tübingen, Germany, adriane.groeger@med.uni-tuebingen.de.

Abstract

A central role of iron in the pathogenesis of Parkinson's disease (PD) has been discussed for many years. Numerous studies using magnetic resonance imaging and transcranial sonography have been performed to detect alterations in tissue iron content of the substantia nigra. This manuscript reviews the findings of this still controversial issue and indicates that specific abnormalities that are suggested to be related to a disturbance of iron homeostasis may play an early role in the pathogenesis of PD.

Diagnose Parkinson's Over the Phone

Max Littles TED Talk
http://www.ted.com/talks/max_little_a_test_for_parkinson_s_with_a_phone_call.html

Palliative care for advanced Parkinson disease: An interdisciplinary clinic and new scale, the ESAS-PD

Parkinsonism Relat Disord. 2012 Aug 3. [Epub ahead of print]

Miyasaki JM, Long J, Mancini D, Moro E, Fox SH, Lang AE, Marras C, Chen R, Strafella A, Arshinoff R, Ghoche R, Hui J.

Source

The Palliative Program for Parkinson Disease and Related Disorders, The Morton and Gloria Shulman Movement Disorders Centre, Toronto Western Hospital, University of Toronto, Canada.

Abstract

Palliative care provides a holistic approach to symptom relief using a multidisciplinary team approach to enhance quality of life throughout the entire course of a particular illness. The care team consists of movement disorders neurologist, a palliative care physician, a wound care nurse, a spiritual counselor and a care coordinator. Palliative care concepts were applied to a group of advanced Parkinson disease (PD) patients in a dedicated Palliative Care Clinic.

METHODS:

A modified Edmonton Symptom Assessment System Scale for PD (ESAS-PD) was developed and applied to 65 PD patients at their initial consultation and following recommended interventions. Scores were compared to those of metastatic cancer patients reported in the palliative care literature.

RESULTS:

The ESAS-PD scores significantly improved after the interventions (56 and 40 respectively, p = 0.0001). The most improved items were constipation, dysphagia, anxiety, pain and drowsiness. ESAS-PD scores were not significantly different from metastatic cancer patients' ESAS scores.

CONCLUSIONS:

ESAS-PD is a quick, effective scale for assessment of late stage PD symptoms. Scores are sensitive to intervention, and therefore have potential clinical utility for physicians and other healthcare providers. Advanced PD patients have a similar degree of symptoms as metastatic cancer patients, respond to treatment in a similar way, and therefore should have access to palliative care services.

Physiotherapy intervention in Parkinson's disease: systematic review and meta-analysis

BMJ. 2012 Aug 6;345:e5004. doi: 10.1136/bmj.e5004.

Tomlinson CL, Patel S, Meek C, Herd CP, Clarke CE, Stowe R, Shah L, Sackley C, Deane KH, Wheatley K, Ives N.

Source

Birmingham Clinical Trials Unit, University of Birmingham, Birmingham B15 2TT, UK.

Abstract

OBJECTIVE:

To assess the effectiveness of physiotherapy compared with no intervention in patients with Parkinson's disease.

DESIGN:

Systematic review and meta-analysis of randomised controlled trials.

DATA SOURCES:

Literature databases, trial registries, journals, abstract books, and conference proceedings, and reference lists, searched up to the end of January 2012.

REVIEW METHODS:

Randomised controlled trials comparing physiotherapy with no intervention in patients with Parkinson's disease were eligible. Two authors independently abstracted data from each trial. Standard meta-analysis methods were used to assess the effectiveness of physiotherapy compared with no intervention. Tests for heterogeneity were used to assess for differences in treatment effect across different physiotherapy interventions used. Outcome measures were gait, functional mobility and balance, falls, clinician rated impairment and disability measures, patient rated quality of life, adverse events, compliance, and economic analysis outcomes.

RESULTS:

39 trials of 1827 participants met the inclusion criteria, of which 29 trials provided data for the meta-analyses. Significant benefit from physiotherapy was reported for nine of 18 outcomes assessed. Outcomes which may be clinically significant were speed (0.04 m/s, 95% confidence interval 0.02 to 0.06, P<0.001), Berg balance scale (3.71 points, 2.30 to 5.11, P<0.001), and scores on the unified Parkinson's disease rating scale (total score -6.15 points, -8.57 to -3.73, P<0.001; activities of daily living subscore -1.36, -2.41 to -0.30, P=0.01; motor subscore -5.01, -6.30 to -3.72, P<0.001). Indirect comparisons of the different physiotherapy interventions found no evidence that the treatment effect differed across the interventions for any outcomes assessed, apart from motor subscores on the unified Parkinson's disease rating scale (in which one trial was found to be the cause of the heterogeneity).

CONCLUSIONS:

Physiotherapy has short term benefits in Parkinson's disease. A wide range of physiotherapy techniques are currently used to treat Parkinson's disease, with little difference in treatment effects. Large, well designed, randomised controlled trials with improved methodology and reporting are needed to assess the efficacy and cost effectiveness of physiotherapy for treating Parkinson's disease in the longer term.

Caffeine for treatment of Parkinson disease: A randomized controlled trial

Neurology. 2012 Aug 1. [Epub ahead of print]

Postuma RB, Lang AE, Munhoz RP, Charland K, Pelletier A, Moscovich M, Filla L, Zanatta D, Romenets SR, Altman R, Chuang R, Shah B.

Source

From the Department of Neurology (R.B.P., A.P., S.R.R., R.A.), McGill University, Montreal General Hospital, Montreal; Morton and Gloria Shulman Movement Disorders Center and the Edmond J. Safra Program in Parkinson's Disease (A.E.L., R.C., B.S.), Toronto Western Hospital, University of Toronto, Toronto, Canada; Pontifical Catholic University of Parana (R.P.M., M.M., L.F., D.Z.), Curitiba, Brazil; Epidemiology, Biostatistics and Occupational Health (K.C.), McGill University, Montreal; and Neuroepidemiology Research Unit (A.P.), Research Institute of the McGill University Health Centre, Montreal, Canada.

Abstract

OBJECTIVE:

Epidemiologic studies consistently link caffeine, a nonselective adenosine antagonist, to lower risk of Parkinson disease (PD). However, the symptomatic effects of caffeine in PD have not been adequately evaluated.

METHODS:

We conducted a 6-week randomized controlled trial of caffeine in PD to assess effects upon daytime somnolence, motor severity, and other nonmotor features. Patients with PD with daytime somnolence (Epworth >10) were given caffeine 100 mg twice daily ×3 weeks, then 200 mg twice daily ×3 weeks, or matching placebo. The primary outcome was the Epworth Sleepiness Scale score. Secondary outcomes included motor severity, sleep markers, fatigue, depression, and quality of life. Effects of caffeine were analyzed with Bayesian hierarchical models, adjusting for study site, baseline scores, age, and sex.

RESULTS:

Of 61 patients, 31 were randomized to placebo and 30 to caffeine. On the primary intention-to-treat analysis, caffeine resulted in a nonsignificant reduction in Epworth Sleepiness Scale score (-1.71 points; 95% confidence interval [CI] -3.57, 0.13). However, somnolence improved on the Clinical Global Impression of Change (+0.64; 0.16, 1.13, intention-to-treat), with significant reduction in Epworth Sleepiness Scale score on per-protocol analysis (-1.97; -3.87, -0.05). Caffeine reduced the total Unified Parkinson's Disease Rating Scale score (-4.69 points; -7.7, -1.6) and the objective motor component (-3.15 points; -5.50, -0.83). Other than modest improvement in global health measures, there were no changes in quality of life, depression, or sleep quality. Adverse events were comparable in caffeine and placebo groups.

CONCLUSIONS:

Caffeine provided only equivocal borderline improvement in excessive somnolence in PD, but improved objective motor measures. These potential motor benefits suggest that a larger long-term trial of caffeine is warranted.Classification of evidence:This study provides Class I evidence that caffeine, up to 200 mg BID for 6 weeks, had no significant benefit on excessive daytime sleepiness in patients with PD.

The PRIPS study: screening battery for subjects at risk for Parkinson's disease

Eur J Neurol. 2012 Aug 1. doi: 10.1111/j.1468-1331.2012.03798.x. [Epub ahead of print]

Berg D, Godau J, Seppi K, Behnke S, Liepelt-Scarfone I, Lerche S, Stockner H, Gaenslen A, Mahlknecht P, Huber H, Srulijes K, Klenk J, Fassbender K, Maetzler W, Poewe W; the PRIPS study group.

Source

Department of Neurodegeneration, Hertie Institute for Clinical Brain Research, Tübingen, Germany; German Center for Neurodegenerative Diseases, Tübingen, Germany.

Abstract

BACKGROUND:

Screening batteries to narrow down a target-at-risk population are essential for trials testing neuroprotective compounds aiming to delay or prevent onset of Parkinson's disease (PD).

METHODS:

The PRIPS study focuses on early detection of incident PD in 1847 at baseline PD-free subjects, and assessed age, male gender, positive family history, hyposmia, subtle motor impairment and enlarged substantia nigra hyperechogenicity (SN+).

RESULTS:

After 3 years follow-up 11 subjects had developed PD. In this analysis of the secondary outcome parameters, sensitivity and specificity of baseline markers for incident PD were calculated in 1352 subjects with complete datasets (10 PD patients). The best approach for prediction of incident PD comprised three steps: (i) prescreening for age, (ii) primary screening for positive family history and/or hyposmia, and (iii) secondary screening for SN+.

CONCLUSION:

With this approach, one out of 16 positively screened participants developed PD compared to one out of 135 in the original cohort. This corresponds to a sensitivity of 80.0%, a specificity of 90.6% and a positive predictive value of 6.1%. These values are higher than for any single screening instrument but still too low for a feasible and cost-effective screening strategy which might require longer follow-up intervals and application of additional instruments.

On the origin of tremor in Parkinson's disease

PLoS One. 2012;7(7):e41598. Epub 2012 Jul 27.

Dovzhenok A, Rubchinsky LL.

Source

Department of Mathematical Sciences and Center for Mathematical Biosciences, Indiana University Purdue University Indianapolis, Indianapolis, Indiana, United States of America.

Abstract

The exact origin of tremor in Parkinson's disease remains unknown. We explain why the existing data converge on the basal ganglia-thalamo-cortical loop as a tremor generator and consider a conductance-based model of subthalamo-pallidal circuits embedded into a simplified representation of the basal ganglia-thalamo-cortical circuit to investigate the dynamics of this loop. We show how variation of the strength of dopamine-modulated connections in the basal ganglia-thalamo-cortical loop (representing the decreasing dopamine level in Parkinson's disease) leads to the occurrence of tremor-like burst firing. These tremor-like oscillations are suppressed when the connections are modulated back to represent a higher dopamine level (as it would be the case in dopaminergic therapy), as well as when the basal ganglia-thalamo-cortical loop is broken (as would be the case for ablative anti-parkinsonian surgeries). Thus, the proposed model provides an explanation for the basal ganglia-thalamo-cortical loop mechanism of tremor generation. The strengthening of the loop leads to tremor oscillations, while the weakening or disconnection of the loop suppresses them. The loop origin of parkinsonian tremor also suggests that new tremor-suppression therapies may have anatomical targets in different cortical and subcortical areas as long as they are within the basal ganglia-thalamo-cortical loop.

Expression pattern and localization of alpha-synuclein in the human enteric nervous system

Neurobiol Dis. 2012 Jul 28. [Epub ahead of print]

Böttner M, Zorenkov D, Hellwig I, Barrenschee M, Harde J, Fricke T, Deuschl G, Egberts JH, Becker T, Fritscher-Ravens A, Arlt A, Wedel T.

Source

Department of Anatomy, Christian Albrecht´s University, Otto-Hahn-Platz 8, 24118 Kiel, Germany.

Abstract

BACKGROUND:

Alpha-synuclein (α-syn) is abundantly expressed in the central nervous system and involved in the regulation of neurotransmission. Insoluble fibrils of phosphorylated α-synuclein (p-α-syn) have been implicated in several neurodegenerative diseases (e.g. Parkinson´s disease, Alzheimer´s disease). The aim of the study was to determine the gene expression pattern and localization of α-syn/p-α-syn in the human enteric nervous system (ENS).

METHODS:

Human colonic specimens (n=13, 15-83 y) were processed for α-syn and p-α-syn immunohistochemistry. Colocalization of α-syn was assessed by dual-labeling with pan-neuronal markers (PGP 9.5, HuC/D). For qPCR studies, tissue was obtained from full-thickness sections, tunica muscularis, submucosa, mucosa, and laser-microdissected (LMD) enteric ganglia.

RESULTS:

Highest α-syn levels were detectable within the tunica muscularis and submucosa. Ganglia isolated by LMD showed high expression of α-syn mRNA. All myenteric and submucosal ganglia and nerve fibers were immunoreactive for α-syn. Dual-labeling revealed colocalization of α-syn with both pan-neuronal markers. p-α-syn immunoreactivity was consistently observed in specimens from adults with increasing age.

CONCLUSIONS:

α-syn is abundantly expressed in all nerve plexus of the human ENS including both neuronal somata and processes. The presence of p-α-syn within the ENS is a regular finding in adults with increasing age and may not be regarded as pathological correlate. The data provide a basis to unravel the functions of α-syn and to evaluate altered α-syn in enteric neuropathies and α-synucleinopathies of the CNS with gastrointestinal manifestations.

Objective and subjective analysis of women's voice with idiopathic Parkinson's disease

Arq Neuropsiquiatr. 2012 Jul;70(7):492-6.

Graças RR, Gama AC, Cardoso FE, Lopes BP, Bassi IB.

 

Abstract

OBJECTIVE:

To compare the voice quality of women with idiopathic Parkinson's disease and those without it.

METHODS:

An evaluation was performed including 19 female patients diagnosed with idiopathic Parkinson's disease, with an average age of 66 years, and 27 women with an average of 67 years-old in the Control Group. The assessment was performed by computed acoustic analysis and perceptual evaluation.

RESULTS:

Parkinson's disease patients presented moderate rough and unstable voice quality. The parameters of grade, roughness, and instability had higher scores in Parkinson's disease patients with statistically significant differences. Acoustic measures of Jitter and period perturbation quotient (PPQ) significantly differ between groups.

CONCLUSIONS:

Parkinson's disease female individuals showed more vocal alterations compared to the Control Group, when both perceptual and acoustic evaluations were analyzed.

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Parkinson disease: Associated disorders in the Norwegian population based incident ParkWest study

Parkinsonism Relat Disord. 2012 Jul 26. [Epub ahead of print]

Skeie GO, Muller B, Haugarvoll K, Larsen JP, Tysnes OB.

 

Source

Department of Neurology, Haukeland University Hospital, 5021 Bergen, Norway.

 

Abstract

Parkinson's disease (PD) may be associated with a number of different diseases due to common risk factors or overlapping symptomatology. We have asked for possible associated disorders in a Norwegian population of incident PD patients and controls, the Norwegian ParkWest study. The patients were diagnosed according to the Gelb criteria. 212 incident PD patients and 175 age and gender matched controls were included. PD patients and controls were asked for information on earlier medical history and family history. PD patients had a higher frequency of self-reported symptoms of depression (p = 0.003) and anxiety disorders (p = 0.004) before baseline. They tended to have a higher frequency of diabetes (p = 0.09) and had a higher frequency of prior stroke or TIA (p = 0.004).

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Comparison study of olfactory function and substantia nigra hyperechogenicity in idiopathic REM sleep behavior disorder, Parkinson's disease and normal control

Neurol Sci. 2012 Jul 28. [Epub ahead of print]

Shin HY, Joo EY, Kim ST, Dhong HJ, Cho JW.

 

Source

Department of Center for Health Promotion, Samsung Medical Center, Sungkyunkwan University School of Medicine, Seoul, Korea.

 

Abstract

Rapid eye movement (REM) sleep behavior disorder (RBD) is a preclinical feature of synucleinopathies, such as Parkinson's disease (PD).This study aimed to investigate the presence of potential early manifestations of parkinsonism, such as olfactory dysfunction and substantia nigra (SN) hyperechogenicity, in idiopathic RBD (iRBD) patients, PD patients and normal controls. We performed an olfactory function test using the cross-cultural smell identification test (CC-SIT) and midbrain transcranial sonography (TCS) in 15 patients with iRBD as confirmed by polysomnography, 30 patients with PD, and 30 normal controls. The CC-SIT scores of the iRBD patients and PD patients were significantly lower than those of the normal controls and similar between iRBD and PD (mean ± SD, 7.1 ± 2.2 and 7.6 ± 2.4 vs. 10.4 ± 1.2, respectively, p < 0.01). The sum of bilateral SN echosignals in the iRBD patients was greater than that of the normal controls but lower than that of the PD patients (0.29 ± 0.47, 0.11 ± 0.17 and 0.72 ± 0.41 cm(2), respectively, p < 0.01). In conclusion, we found that the concomitant abnormality of olfaction and increased SN echogenicity was more frequent in iRBD compared with normal control. Olfactory dysfunction and SN hyperechogenicity could be preclinical manifestations of parkinsonism in iRBD patients.

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Novel One-Step Immunoassays to Quantify α-Synuclein: Applications for Biomarker Development and High-Throughput Screening

J Biol Chem. 2012 Jul 27. [Epub ahead of print]

Bidinosti M, Shimshek DR, Mollenhauer B, Marcellin D, Schweizer T, Lotz GP, Schlossmacher MG, Weiss A.


 

Source

Novartis Institutes for BioMedical Research, Switzerland;

 

Abstract

Familial Parkinson's disease (PD) can result from α-synuclein gene multiplication, implicating the reduction of neuronal α-synuclein as a therapeutic target. Moreover, α-synuclein content in human cerebrospinal fluid (CSF) represents a PD biomarker candidate. However, capture-based assays for α-synuclein quantification in CSF (such as by ELISA) have shown discrepancies and have limited suitability for high-throughput screening. Here, we describe two sensitive, in-solution, time-resolved Forster's resonance energy transfer (TR-FRET)-based immunoassays for total and oligomeric α-synuclein quantification. CSF analysis showed strong concordance for total α-synuclein content between two TR-FRET assays and, in agreement with a previously characterized 36 hour protocol-based ELISA, demonstrated lower α-synuclein levels in PD donors. Critically, the assay's suitability for high-throughput screening of siRNA constructs and small molecules aimed at reducing endogenous α-synuclein levels was established and validated. In a small-scale proof of concept compound screen using 384 well plates, signals ranged from <30 to >120 percent of the mean of vehicle-treated cells for molecules known to lower and increase cellular α-synuclein, respectively. Further, a reverse genetic screen of a kinase-directed siRNA library identified seven genes that modulated α-synuclein protein levels (five whose knock-down increased and two which decreased cellular α-synuclein protein). This provides critical new biological insight into cellular pathways regulating α-synuclein steady-state expression, which may help guide further drug disovery efforts. Moreover, we describe an inherent limitation in current α-synuclein oligomer detection methodology, a finding which will direct improvement of future assay design. Our one-step TR-FRET-based platform for α-synuclein quantification provides a novel platform with superior performance parameters for the rapid screening of large biomarker cohorts and of compound and genetic libraries, both of which are essential to the development of PD therapies.

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