Parkinson Disease: England

Schrag A, Barone P, Brown RG, Leentjens AF, McDonald WM, Starkstein S, Weintraub D, Poewe W, Rascol O, Sampaio C, Stebbins GT, Goetz CG. · University Department of Clinical Neurosciences, Royal Free and University College Medical School, London, UK. · Mov Disord. · Pubmed #17394234 links to  free full text

Abstract: Depression is a common comorbid condition in Parkinson's disease (PD) and a major contributor to poor quality of life and disability. However, depression can be difficult to assess in patients with PD due to overlapping symptoms and difficulties in the assessment of depression in cognitively impaired patients. As several rating scales have been used to assess depression in PD (dPD), the Movement Disorder Society commissioned a task force to assess their clinimetric properties and make clinical recommendations regarding their use. A systematic literature review was conducted to explore the use of depression scales in PD and determine which scales should be selected for this review. The scales reviewed were the Beck Depression Inventory (BDI), Hamilton Depression Scale (Ham-D), Hospital Anxiety and Depression Scale (HADS), Zung Self-Rating Depression Scale (SDS), Geriatric Depression Scale (GDS), Montgomery-Asberg Depression Rating Scale (MADRS), Unified Parkinson's Disease Rating Scale (UPDRS) Part I, Cornell Scale for the Assessment of Depression in Dementia (CSDD), and the Center for Epidemiologic Studies Depression Scale (CES-D). Seven clinical researchers with clinical and research experience in the assessment of dPD were assigned to review the scales using a structured format. The most appropriate scale is dependent on the clinical or research goal. However, observer-rated scales are preferred if the study or clinical situation permits. For screening purposes, the HAM-D, BDI, HADS, MADRS, and GDS are valid in dPD. The CES-D and CSDD are alternative instruments that need validation in dPD. For measurement of severity of depressive symptoms, the Ham-D, MADRS, BDI, and SDS scales are recommended. Further studies are needed to validate the CSDD, which could be particularly useful for the assessment of severity of dPD in patients with comorbid dementia. To account for overlapping motor and nonmotor symptoms of depression, adjusted instrument cutoff scores may be needed for dPD, and scales to assess severity of motor symptoms (e.g., UPDRS) should also be included to help adjust for confounding factors. The HADS and the GDS include limited motor symptom assessment and may, therefore, be most useful in rating depression severity across a range of PD severity; however, these scales appear insensitive in severe depression. The complex and time-consuming task of developing a new scale to measure depression specifically for patients with PD is currently not warranted.

McKeith IG, Dickson DW, Lowe J, Emre M, O'Brien JT, Feldman H, Cummings J, Duda JE, Lippa C, Perry EK, Aarsland D, Arai H, Ballard CG, Boeve B, Burn DJ, Costa D, Del Ser T, Dubois B, Galasko D, Gauthier S, Goetz CG, Gomez-Tortosa E, Halliday G, Hansen LA, Hardy J, Iwatsubo T, Kalaria RN, Kaufer D, Kenny RA, Korczyn A, Kosaka K, Lee VM, Lees A, Litvan I, Londos E, Lopez OL, Minoshima S, Mizuno Y, Molina JA, Mukaetova-Ladinska EB, Pasquier F, Perry RH, Schulz JB, Trojanowski JQ, Yamada M, Anonymous00346. · Institute for Ageing and Health, University of Newcastle upon Tyne, UK. · Neurology. · Pubmed #16237129 No free full text.

Abstract: The dementia with Lewy bodies (DLB) Consortium has revised criteria for the clinical and pathologic diagnosis of DLB incorporating new information about the core clinical features and suggesting improved methods to assess them. REM sleep behavior disorder, severe neuroleptic sensitivity, and reduced striatal dopamine transporter activity on functional neuroimaging are given greater diagnostic weighting as features suggestive of a DLB diagnosis. The 1-year rule distinguishing between DLB and Parkinson disease with dementia may be difficult to apply in clinical settings and in such cases the term most appropriate to each individual patient should be used. Generic terms such as Lewy body (LB) disease are often helpful. The authors propose a new scheme for the pathologic assessment of LBs and Lewy neurites (LN) using alpha-synuclein immunohistochemistry and semiquantitative grading of lesion density, with the pattern of regional involvement being more important than total LB count. The new criteria take into account both Lewy-related and Alzheimer disease (AD)-type pathology to allocate a probability that these are associated with the clinical DLB syndrome. Finally, the authors suggest patient management guidelines including the need for accurate diagnosis, a target symptom approach, and use of appropriate outcome measures. There is limited evidence about specific interventions but available data suggest only a partial response of motor symptoms to levodopa: severe sensitivity to typical and atypical antipsychotics in approximately 50%, and improvements in attention, visual hallucinations, and sleep disorders with cholinesterase inhibitors.

Grosset DG, Schapira AH. · Institute of Neurological Sciences, Department of Neurology, Southern General Hospital, 1345 Govan Rd, Glasgow G51 4TF, UK. · J Neurol Neurosurg Psychiatry. · Pubmed #18487552 No free full text.

This publication has no abstract.

Chaudhuri KR, Schapira AH. · National Parkinson Foundation Centre of Excellence, King's College Hospital and University Hospital Lewisham, London, UK. · Lancet Neurol. · Pubmed #19375664 No free full text.

Abstract: Several studies, including work from the Parkinson's disease (PD) non-motor group and others, have established that the non-motor symptoms of PD are common, occur across all stages of PD, are under-reported, and are a key determinant of quality of life. Research suggests that the non-motor symptoms of the disease are frequently unrecognised by clinicians and remain untreated. Even when identified, there is a common perception that many of these symptoms are untreatable. The role of dopaminergic drugs in treating the various non-motor problems of PD, although clinically recognised, has received little attention. In this Review, we investigate the dopaminergic basis of the range of non-motor symptoms that occur in PD such as depression, apathy, sleep disorders (including rapid-eye movement sleep behaviour disorder), and erectile dysfunction. We discuss the evidence that these symptoms are treatable, at least in part, with various dopaminergic strategies and, where relevant, we also refer to the use of deep-brain stimulation of appropriate targets in the brain. This Review provides a comprehensive overview of the management of this challenging aspect of PD.

Archibald NK, Clarke MP, Mosimann UP, Burn DJ. · Clinical Research Fellow, Clinical Ageing Research Unit, Newcastle University, Campus for Ageing and Vitality, Newcastle upon Tyne, NE4 5PL, UK. · Brain. · Pubmed #19336464 No free full text.

Abstract: As a more complete picture of the clinical phenotype of Parkinson's disease emerges, non-motor symptoms have become increasingly studied. Prominent among these non-motor phenomena are mood disturbance, cognitive decline and dementia, sleep disorders, hyposmia and autonomic failure. In addition, visual symptoms are common, ranging from complaints of dry eyes and reading difficulties, through to perceptual disturbances (feelings of presence and passage) and complex visual hallucinations. Such visual symptoms are a considerable cause of morbidity in Parkinson's disease and, with respect to visual hallucinations, are an important predictor of cognitive decline as well as institutional care and mortality. Evidence exists of visual dysfunction at several levels of the visual pathway in Parkinson's disease. This includes psychophysical, electrophysiological and morphological evidence of disruption of retinal structure and function, in addition to disorders of 'higher' (cortical) visual processing. In this review, we will draw together work from animal and human studies in an attempt to provide an insight into how Parkinson's disease affects the retina and how these changes might contribute to the visual symptoms experienced by patients.

Dobbs RJ, Dobbs SM, Weller C, Charlett A, Bjarnason IT, Curry A, Ellis DS, Ibrahim MA, McCrossan MV, O'Donohue J, Owen RJ, Oxlade NL, Price AB, Sanderson JD, Sudhanva M, Williams J. · Section of Clinical Neuropharmacology, Institute of Psychiatry, King's College London, London, UK. or · Helicobacter. · Pubmed #19250506 No free full text.

Abstract: We challenge the concept of idiopathic parkinsonism (IP) as inevitably progressive neurodegeneration, proposing a natural history of sequential microbial insults with predisposing host response. Proof-of-principle that infection can contribute to IP was provided by case studies and a placebo-controlled efficacy study of Helicobacter eradication. "Malignant" IP appears converted to "benign", but marked deterioration accompanies failure. Similar benefit on brady/hypokinesia from eradicating "low-density" infection favors autoimmunity. Although a minority of UK probands are urea breath test positive for Helicobacter, the predicted probability of having the parkinsonian label depends on the serum H. pylori antibody profile, with clinically relevant gradients between this "discriminant index" and disease burden and progression. In IP, H. pylori antibodies discriminate for persistently abnormal bowel function, and specific abnormal duodenal enterocyte mitochondrial morphology is described in relation to H. pylori infection. Slow intestinal transit manifests as constipation from the prodrome. Diarrhea may flag secondary small-intestinal bacterial overgrowth. This, coupled with genetically determined intense inflammatory response, might explain evolution from brady/hypokinetic to rigidity-predominant parkinsonism.

Schapira AH. · University Department of Clinical Neurosciences, Institute of Neurology, University College London, London, NW3 2PF, UK. · Neurology. · Pubmed #19221314 No free full text.

Abstract: During the last 20 years, an enormous research effort and hundreds of millions of dollars have been spent attempting to develop and prove that drugs may slow the rate of progression of Parkinson disease (PD). At the time of writing, no drug has yet satisfied the rigorous criteria set by clinicians and licensing authorities for a neuroprotective agent. Despite this apparent failure, numerous important lessons have been learned, and some areas for optimism have emerged. Dopaminergic drugs have, for 40 years, been the basis for the treatment of the predominant early motor features of PD. Several of these drugs have also demonstrated an ability to protect cells, including neurons, against a range of toxins that are of relevance to the pathogenesis of PD. Some have entered clinical trials for neuroprotection, and a few have produced a positive result according to the endpoint selected. The interpretation of these trials is the subject of some debate. A pattern has emerged in these and other clinical trials, which has lead to a novel concept for neuroprotection, and that is simply to treat early rather than delay. The basis for this may lie in the support of basal ganglia compensatory mechanisms and the restoration of normal dopaminergic transmission.

Lees AJ. · Reta Lila Weston Institute for Neurological Studies, Institute of Neurology, UCL and the National Hospital for Neurology and Neurosurgery, Queen Square, London. · Neurology. · Pubmed #19221309 No free full text.

Abstract: Although our concepts of what causes Parkinson disease (PD) are ever changing and the hunt for a reliable biomarker continues, the clinical picture remains as distinctive as when the malady was first described by James Parkinson and the neurologic Grand Masters of the nineteenth century. Hyposmia and visual hallucinations, however, can now be added as additional features of the clinical syndrome which may be helpful in distinguishing PD from atypical parkinsonism, as well as the growing list of causes of secondary parkinsonism. Selective vulnerability of catecholaminergic long axon projection neurons (part of the isodendritic core) in PD is an important, if recently somewhat neglected, fact and correlation of the severity of nigral loss with bradykinesia and rigidity is the only very reliable anatomo-clinical correlation. Although the Lewy body seems to be closely linked with our notion of PD as a clinicopathologic nosological entity, its role in the pathogenesis of the disorder is still obscure and hotly debated. Its presence in some of the long-surviving grafted neurons in fetal implants may provide important insights into its role in the disease process. Although Braak's hypothesis implicating the medulla oblongata as an obligate trigger for the subsequent spread of the pathologic process has generated much interest and encouraged more research, it seems unlikely as an explanation for the natural history of PD.

O'Sullivan SS, Evans AH, Lees AJ. · Reta Lila Weston Institute of Neurological Studies, Institute of Neurology, University College London, London, England. · CNS Drugs. · Pubmed #19173374 No free full text.

Abstract: Dopamine dysregulation syndrome (DDS) is a relatively recently described iatrogenic disturbance that may complicate long-term symptomatic therapy of Parkinson's disease. Patients with DDS develop an addictive pattern of dopamine replacement therapy (DRT) use, administering doses in excess of those required to control their motor symptoms. The prevalence of DDS in patients attending specialist Parkinson's disease centres is 3-4%. Amongst the behavioural disturbances associated with DDS are punding, which is a complex stereotyped behaviour, and impulse control disorders (ICDs), such as pathological gambling, hypersexuality, compulsive shopping and compulsive eating. We review the risk factors and potential mechanisms for the development of DDS, including personality traits, potential genetic influences and Parkinson's disease-related cognitive deficits. Impulsive personality traits are prominent in patients developing DDS, and have been previously associated with the development of substance dependence. Candidate genes affecting the dopamine 'D(2)-like' receptor family have been associated with impulsive personality traits in addition to drug and nondrug addictions. Impaired decision making is implicated in addictive behaviours, and decision-making abilities can be influenced by dopaminergic medications. In Parkinson's disease, disruption of the reciprocal loops between the striatum and structures in the prefrontal cortex following dopamine depletion may predispose to DDS. The role of DRT in DDS is discussed, with particular reference to models of addiction, suggesting that compulsive drug use is due to progressive neuroadaptations in dopamine projections to the accumbens-related circuitry. Evidence for neuroadaptations and sensitization occurring in DDS include enhanced levodopa-induced ventral striatal dopamine release. Levodopa is still considered the most potent trigger for DDS in Parkinson's disease, but subcutaneous apomorphine and oral dopamine agonists may also be responsible. In the management of DDS, further research is needed to identify at-risk groups, thereby facilitating more effective early intervention. Therefore, an increased awareness of the syndrome amongst treating physicians is vital. Medication reduction strategies are employed, particularly with regard to avoiding rapidly acting 'booster' DRT formulations. Psychosocial treatments, including cognitive-behavioural therapy, have been beneficial in treating substance use disorders and ICDs in non-Parkinson's disease patients, but there are currently no published trials of psychological interventions in DDS. Further studies are also required to identify factors that can predict those patients with DDS or ICDs who will derive benefit from surgical interventions such as deep brain stimulation.

Graeber MB. · The Athenaeum, Pall Mall, London SW1Y 5ER, UK. · Exp Neurol. · Pubmed #19166835 No free full text.

Abstract: With the advent of systems biological concepts there has been a surge of interest in biological factors, or biomarkers that can be measured and which allow the identification of individuals at risk. Biomarkers for Parkinson's disease have been identified which provide evidence of systemic metabolic dysregulation in this disorder. Such biomarkers can be studied in blood, serum and plasma but also in CSF and urine, and the study by Hoepken et al. in this issue has even made use of skin fibroblasts. The authors report on the induction of alpha-synuclein expression and suggest that the expression changes described might potentially allow objective PD patient diagnosis in an accessible, peripheral tissue. This mini-review aims to provide a broader perspective on PD functional genomics and seeks to illustrate in a systems biological context why the findings by Hoepken and colleagues are of clinical significance.

Lewis PA. · Department of Molecular Neuroscience, Institute of Neurology, University College London, UK. · Biol Cell. · Pubmed #19152505 No free full text.

Abstract: The ROCO family of multidomain proteins extends across the eukaryotes, and has been implicated in numerous cellular processes. Following the description of mutations causing PD (Parkinson's disease) in a human representative of the ROCO family, LRRK2 (leucine-rich repeat kinase 2), a great deal of research has been carried out into these proteins. This review examines the published data regarding the roles the ROCO proteins are thought to play in cell processes, and how the structure and domain organization of these proteins relates to their function.

Yang YX, Wood NW, Latchman DS. · Medical Molecular Biology Unit, Institute of Child Health, University College London, London, UK. · Neuroreport. · Pubmed #19151598 No free full text.

Abstract: Parkinson's disease is the second most common neurodegenerative disorder and remains incurable. Considerable progress has been made in understanding the molecular mechanisms of this disease, in particular, a distinct set of genes have emerged, whose dysfunctional regulation is strongly associated with the condition. These genes include alpha-synuclein, parkin, PTEN induced Putative Kinase 1 (PINK1), DJ-1, Leucine Rich Repeat Kinase 2 (LRRK2) and ATP13A2. Here we discuss what has been learnt in the study of these genes and how these genes may contribute to the pathogenesis of Parkinson's disease through different molecular pathways, and consider how these pathways might converge to lead to the onset of Parkinson's disease.

Steiger M, Jost W, Grandas F, Van Camp G. · The Walton Centre for Neurology and Neurosurgery, Fazakerley, Liverpool, UK. · J Neural Transm. · Pubmed #19142570 No free full text.

Abstract: A literature review was conducted to assess risk of cardiac valve regurgitation (CVR) associated with use of ergot-derived and non-ergot dopamine agonists (DAs) in patients with Parkinson's disease (PD). Inclusion criteria: case-control/observational studies of >10 patients with PD treated with DAs, including a control group and assessment of incidence/risk of CVR. Of the 166 publications identified, 14 met all inclusion criteria and included 1,750 patients. In 11 of the studies, a significant increase in CVR frequency of any severity (at the aortic, mitral or tricuspid valve) in the ergot group vs. the non-ergot or control group was described. No study reported increased risk of CVR for non-ergot DAs, compared with controls. In the studies identified in the literature, the use of ergot-derived DAs (pergolide and cabergoline) in patients with PD was associated with increased risk of CVR. Increased risk of CVR was not associated with the use of non-ergot DAs.

Jenner P. · Neurodegenerative Disease Research Centre, School of Health and Biomedical Sciences, King's College, London, United Kingdom. · Ann Neurol. · Pubmed #19127585 No free full text.

Abstract: Functional models of Parkinson's disease (PD) have led to effective treatment for the motor symptoms. Toxin-based models, such as the 6-hydroxydopamine-lesioned rat and 1-methyl-4-phenyl-1,2,3,6-tetrahydropyridine-treated primate, have resulted in novel dopaminergic therapies and new therapeutic strategies. They have also been used to study processes underlying motor complications, particularly dyskinesia, and for developing pharmacological approaches to dyskinesia avoidance and suppression. Symptomatic models of PD based on nigrostriatal degeneration have a high degree of predictability of clinical effect of dopaminergic drugs on motor symptoms in humans. However, the effects of nondopaminergic drugs in these models do not translate effectively into clinical efficacy. Newer experimental models of PD have attempted to reproduce the pathogenic process and to involve all areas of the brain pathologically affected in humans. In addition, models showing progressive neuronal death have been sought but so far unsuccessfully. Pathogenic modeling has been attempted using a range of toxins, as well as through the use of transgenic models of gene defects in familial PD and mutant rodent strains. However, there are still no accepted progressive models of PD that mimic the processes known to occur during cell death and that result in the motor deficits, pathology, biochemistry, and drug responsiveness as seen in humans. Nevertheless, functional models of PD have led to many advances in treating the motor symptoms of the disorder, and we have been fortunate to have them available. They are an important reason the treatment of PD is so much better compared with treatments for related illnesses.

Antoniades CA, Barker RA. · Cambridge Centre for Brain Repair, Department of Clinical Neurosciences, University of Cambridge, Forvie Site, Cambridge CB22PY, UK. · Expert Rev Neurother. · Pubmed #19086880 No free full text.

Abstract: Parkinson's disease (PD) is a progressive neurodegenerative disorder that primarily presents with features of bradykinesia, rigidity and tremor, and has, as part of its core pathology, the degeneration of dopaminergic neurons in the substantia nigra pars compacta. There is a great need for the development of a reliable diagnostic tool to improve promptness of diagnosis, definition of disease subtypes, and to monitor disease progression and demonstrate treatment efficacy in the case of disease modifying therapies. Current biomarkers range from objective clinical tools, to neuroimaging, to 'wet' markers involving blood and cerebrospinal fluid. To date, all candidate biomarkers for PD have failed to be developed into a clinically useful tool. Ideally, a combination of sensitive markers will be needed, not only to predict the onset of PD, but also to help in subtype classification and to follow progression. Here, we critically review various PD biomarker studies.

Valori CF, Ning K, Wyles M, Azzouz M. · University of Sheffield, Sheffield S10 2RX, UK. · Curr Gene Ther. · Pubmed #19075624 No free full text.

Abstract: Vectors based on non-HIV lentiviruses are opening up new approaches for the treatment of human disorders. These vectors efficiently deliver genes into many different types of cells from a broad range of species including man and the resulting gene expression is long-term. These features make them very attractive to be transformed into tools for gene therapy. HIV-1 based lentiviral vectors were initially developed, a process which provided valuable insights into the biology of these vectors allowing progressive improvement of non-HIV vectors. The latest vectors have been refined to a very high level and can be produced safely for the clinic. This review will describe the general features of lentiviral vectors with particular emphasis on vectors derived from the non-HIV lentiviruses such as equine infectious anaemia virus (EIAV), simian immunodeficiency virus (SIV), and feline immunodeficiency virus (FIV). It will then describe some key examples of gene therapy applications in neurological diseases such as Parkinson's disease (PD), motor neuron diseases, lysosomal storage diseases and ocular disorders. Finally, the prospects for clinical application of non-HIV lentiviral vectors for these disorders will also be outlined.

Grahn JA, Parkinson JA, Owen AM. · MRC Cognition and Brain Sciences Unit, Cambridge, UK. · Behav Brain Res. · Pubmed #19059285 No free full text.

Abstract: In recent years, a common approach to understanding how the basal ganglia contribute to learning and memory in humans has been to study the deficits that occur in patients with basal ganglia pathology, such as Parkinson's disease and Huntington's disease. Pharmacological manipulations in patients and in healthy volunteers have also been conducted to investigate the role of dopamine, a neurotransmitter that is crucial for normal striatal functioning. When combined with powerful functional neuroimaging methods such as positron emission tomography and functional magnetic resonance imaging, such studies can provide important new insights into striatal function and dysfunction in humans. In this review, we consider this broad literature in an attempt to define a specific role for the caudate nucleus in learning and memory, and in particular, how this role may differ from that of the putamen. We conclude that the caudate nucleus contributes to learning and memory through the excitation of correct action schemas and the selection of appropriate sub-goals based on an evaluation of action-outcomes; both processes that are fundamental to all tasks involve goal-directed action.

Schapira AH. · University Department of Clinical Neurosciences, University College London, London NW3 2PF, UK. · Trends Pharmacol Sci. · Pubmed #19042040 No free full text.

Abstract: Parkinson's disease (PD) is the second most common neurodegenerative disorder after Alzheimer's disease and is an important cause of chronic disability. Numerous important advances have been made in our understanding of the aetiopathogenesis, pathology and clinical phenomenology of this disease, and these have underpinned advances in symptomatic treatment and the prospect that these might be extended into interventions that will slow progression. It is notable that the continuing characterisation of the downstream biochemical consequences of the genetic causes of PD serves only to reinforce this notion. Progress in the management of PD has continued, particularly in timing of drug initiation and the sequence and combinations in which drugs are used to improve long-term outcome and reduce drug-induced complications. Particular progress has been made in the field of neuroprotection, where novel therapies and clinical trial designs are being tested. This review will focus particularly upon this area.

Fitzgerald JC, Plun-Favreau H. · Department of Molecular Neuroscience, Institute of Neurology, University College London, UK. · FEBS J. · Pubmed #19021753 No free full text.

Abstract: Rare, inherited mutations causing familial forms of Parkinson's disease have provided insight into the molecular mechanisms that underlie the genetic and sporadic forms of this disease. Loss of protein function resulting from autosomal-recessive mutations in PTEN-induced putative kinase 1 (PINK1), Parkin and DJ-1 has been linked to mitochondrial dysfunction, accumulation of abnormal and misfolded proteins, impaired protein clearance and oxidative stress. Accumulating evidence suggests that wild-type PINK1, Parkin and DJ-1 may be key components of neuroprotective signalling cascades that run in parallel, interact via cross talk or converge in a common pathway.

Devine MJ, Lewis PA. · Department of Clinical Neuroscience, Imperial College London, UK. · FEBS J. · Pubmed #19021752 No free full text.

Abstract: The last decade has seen clear links emerge between the genetic determinants and neuropathological hallmarks of parkinsonism and dementia, notably with the discovery of mutations in alpha-synuclein and tau. Following the description of mutations in LRRK2 linked to Parkinson's disease, characterized by variable pathology including either alpha-synuclein or tau deposition, it has been suggested that LRRK2 functions as an upstream regulator of Parkinson's disease pathogenesis. This minireview explores this model, in the context of our current understanding of the biochemistry of LRRK2, alpha-synuclein and tau.

Tarnaris A, Kitchen ND, Watkins LD. · Victor Horsley Department of Neurosurgery, National Hospital for Neurology and Neurosurgery, London, United Kingdom. · J Neurosurg. · Pubmed #18991499 No free full text.

Abstract: OBJECT: Normal pressure hydrocephalus (NPH) represents a treatable form of dementia. Recent estimates of the incidence of this condition are in the region of 5% of patients with dementia. The symptoms of NPH can vary among individuals and may be confused with those of patients with multi-infarct dementia, dementia of the Alzheimer type, or even Parkinson disease. Traditionally the diagnosis of NPH could only be confirmed postoperatively by a favorable outcome to surgical diversion of CSF. The object of this literature review was to examine the role of structural and functional imaging in providing biomarkers of favorable surgical outcome. METHODS: A Medline search was undertaken for the years 1980-2006, using the following terms: normal pressure hydrocephalus, adult hydrocephalus, chronic hydrocephalus, imaging, neuroimaging, imaging studies, outcomes, surgical outcomes, prognosis, prognostic value, sensitivity, specificity, positive predictive value, negative predictive value, and accuracy. RESULTS: The query revealed 16 studies that correlated imaging with surgical outcomes offering accuracy results. Three studies fulfilled the statistical criteria of a biomarker. A dementia Alzheimer-type pattern on SPECT in patients with idiopathic NPH, the presence of CSF flow void on MR imaging, and the N-acetylaspartate/choline ratio in patients with the secondary form are able to predict surgical outcomes with high accuracy. CONCLUSIONS: There is at present Level A evidence for using MR spectroscopy in patients with secondary NPH, and Level B evidence for using SPECT and phase-contrast MR imaging to select patients with idiopathic NPH for shunt placement. The studies, however, need to be repeated by other groups. The current work should act as a platform to design further studies with larger sample sizes.

Stein JF. · Department of Physiology, Anatomy and Genetics, University of Oxford, OX1 3PT, UK. · Exp Neurol. · Pubmed #18977223 No free full text.

This publication has no abstract.

Benamer HT, Grosset DG. · Department of Neurology, Queen Elizabeth Neuroscience Centre, Queen Elizabeth University Hospital, Birmingham, UK. · Eur Neurol. · Pubmed #18948694 links to  free full text

Abstract: Over the last 75 years there has been continuous debate about the existence of vascular parkinsonism (VP). The condition has been named and renamed several times, with terms such as arteriosclerotic parkinsonism, arteriosclerotic pseudo-parkinsonism and lower-body parkinsonism. Despite the progress in our understanding of other parkinsonian syndromes, such as progressive supranuclear palsy and multiple-system atrophy, and significant developments in neuroimaging techniques, the concept of VP is still unclear and the clinical diagnosis is often difficult. There are no widely agreed diagnostic criteria. This article reviews the current literature relating to VP in particular to identify the different clinical presentations that have been described.

Brooks DJ. · Division of Neuroscience and Medical Research Council Clinical Sciences Centre, Imperial College, Hammersmith Hospital, Du Cane Road, London, United Kingdom. · Semin Neurol. · Pubmed #18843572 No free full text.

Abstract: In this article, after providing a description of the technique of brain positron emission tomography (PET), the review focuses on the application of PET and other recent advances of neuroimaging in understanding the structural, pathophysiological, and pharmacological changes associated with Parkinson's disease (PD). In early cases of PD, demonstration of the presence of nigral structural abnormalities with transcranial sonography and striatal dopaminergic dysfunction with functional imaging provides a rationale for the use of dopaminergic medications. The presence of altered striatal signal with diffusion-weighted magnetic resonance imaging (DWI) or reduced lentiform nucleus glucose metabolism with fluorodeoxyglucose PET suggests the presence of an atypical PD variant. Finally, the value of functional imaging as a biomarker for following the progression of PD and for understanding mechanisms of dementia when present is debated.

Chaudhuri KR, Naidu Y. · Kings College Hospital, Denmark Hill, London, UK. · J Neurol. · Pubmed #18787880 No free full text.

Abstract: Non motor symptoms (NMS) of PD are a key determinant of health, quality of life and societal cost of PD. Contrary to common perception, many NMS of PD occur early in PD and some may even predate the diagnosis of PD which is based on motor signs. These include olfactory deficit, sleep problems such as REM behaviour disorder, contipation and the more recently described male erectile dysfunction. The non motor quesionnaire (NMSQuest) and the recently validated NMS scale allow falgging and quantification of NMS of PD and therefore are important tools to comprehensively assess symptom load in PD.