Podcast Script April Special 2012 v1

7/28/2019 Podcast Script April Special 2012 v1

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Script for MDS Journal PodcastVolume 27, Issue 5

HOST: On behalf of the MovementDisorder Society, welcome to our monthly series of

reports on movement disorders research. In this podcast you will hear a reading of the

abstracts from the April 2012 Special Issue: Prodromal Parkinson's Disease of theMovementDisorders Journal.

You can learn more about the work of The MovementDisorder Society at www [dot]movementdisorders [dot] org. To access the MovementDisorders Journal on the web,visit movementdisordersjournal [dot] com

Lewy pathology and neurodegeneration in premotor Parkinson's

disease

Authors: Kelly Del Tredici and Heiko Braak

The foremost motor manifestations of Parkinson's disease are resting tremor, cogwheelrigidity, hypokinesia/bradykinesia, and postural instability. Epidemiological and clinical

data reveal that a wide variety of additional complaints (nonmotor symptoms), also

considerably impair patients' quality of life parallel to the chronic-progressiveneurodegenerative disorder. This article reviews the neuropathology and anatomy of

Lowy pathology-related neurodegeneration in relation to selected nonmotro and

prodromal dysfunctions.

Premotor Parkinson's disease: Concepts and definitions

Authors: Andrew Siderowf and Anthony E. Lang

Parkinson's disease (PD) has a prodromal phase during which nonmotor clinical featuresas well as physiological abnormalities may be present. These premotor markers could be

used to screen for PD before motor abnormalities are present. The technology to identify

PD before it reaches symptomatic Braak Stage 3 (substantia nigra compacta [SNc]

involvement) already exists. The current challenge is to define the appropriate scope of


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use of predictive testing for PD. Imaging technologies such as dopamine transporter

imaging currently offer the highest degree of accuracy for identifying premotor PD, butthey are expensive as screening tools, and abnormalities on these studies would only be

evident at Braak Stage 3 or higher. Efficiency is greatly enhanced by combining imaging

with a prescreening test such as olfactory testing. This 2-step process has the potential to

greatly reduce costs while retaining diagnostic accuracy. Alternatively, or in concert withthis approach, evaluating high-risk populations (eg, patients with rapid eye movement

behavior disorder or LRRK2 mutations) would enrich the sample for cases withunderlying PD. Ultimately, the role of preclinical detection of PD will be determined by

the ability of emerging therapies to influence clinical outcomes. As such, implementation

of large-scale screening strategies awaits the arrival of clearly safe and effective therapiesthat address the underlying pathogenesis of PD. Future research will establish more

definitive biomarkers capable of revealing the presence of disease in advance of SNc

involvement with the promise of the potential for introducing disease-modifying therapy

even before the development of evidence of dopamine deficiency.

Identifying prodromal Parkinson's disease: Pre-Motor disorders in

Parkinson's disease

Authors: Ronald B. Postuma, Dag Aarsland, Paolo Barone, David J. Burn, Christopher H.

Hawkes, Wolfgang Oertel, Tjalf Ziemssen

Increasing recognition that Parkinson's disease (PD) may start outside of the substantia

nigra has led to a rapidly expanding effort to define prodromal stages of PD, before motor

signs permit classical diagnosis. Many of these efforts center around the identification ofclinical non-motor symptoms and signs of disease. There is now direct evidence that

olfaction, rapid eye movement (REM) sleep behavior disorder (RBD), constipation, and

depression can be present in prodromal PD. In addition, there is suggestive evidence thatvisual changes, other autonomic symptoms, and subtle cognitive changes may also be

present at prodromal stages. A critical issue in utility of these prodromal markers will be

assessment of sensitivity, specificity, and positive and negative predictive values.Although these have yet to be fully defined, olfactory deficits, some visual changes, and

autonomic symptoms occur in the majority of PD patients at diagnosis, suggesting good

potential sensitivity. However, with the exception of RBD and perhaps some specificautonomic measures, specificity, and positive predictive value of these markers may be

insufficient to be used alone as identifiers of prodromal disease. The evidence for theutility of olfaction, RBD, autonomic markers, visual changes, mood disorders, andcognitive loss as markers of prodromal PD and the potential sensitivity and specificity of

these markers are summarized.


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Motor signs in the prodromal phase of Parkinson's disease

Authors: Walter Maetzler and Jeffrey M. Hausdorff

Relatively subtle deterioration of the motor system likely occurs well before the patient

meets established motor criteria for a clinical diagnosis of Parkinson's disease; ie, theoccurrence of at least 2 of the cardinal motor deficits: bradykinesia, rigidity, tremor,

and/or postural instability. Powerful compensatory mechanisms may mask these clinical

symptoms and make them difficult to identify and evaluate in the earliest stages of the

illness. This review summarizes our current knowledge of motor signs that are thought tooccur in the prodromal phase of Parkinson's disease and suggests how motor assessment

batteries could be designed to detect these subclinical motor deficits with a high degree of

accuracy and sensitivity.

Neuroimaging: Current role in detecting pre-motor Parkinson's disease

Authors: Jana Godau, Anna Hussl, Praween Lolekha, A. Jon Stoessl, Klaus Seppi

Convergent evidence suggests a pre-motor period in Parkinson's disease (PD) during

which typical motor symptoms have not yet developed although dopaminergic neurons in

the substantia nigra have started to degenerate. Advances in different neuroimaging

techniques have allowed the detection of functional and structural changes in early PD.This review summarizes the state of the art knowledge concerning structural

neuroimaging techniques including magnetic resonance imaging (MRI) and transcranial

B-mode-Doppler-sonography (TCS) as well as functional neuroimaging techniques usingradiotracer imaging (RTI) with different radioligands in detecting pre-motor PD.

Biochemical premotor biomarkers for Parkinson's disease

Authors: Brit Mollenhauer, Jing Zhang

A biomarker is a biological characteristic that is objectively measured and evaluated asan indicator of normal biological or pathologic processes or of pharmacologic responsesto a therapeutic intervention. We reviewed the current status of target protein biomarkers

(eg, total/oligomeric -synuclein and DJ-1) in cerebrospinal fluid, as well as on unbiased

processes that can be used to discover novel biomarkers. We have also provide detailsabout strategies toward potential populations/models and technologies, including the need

for standardized sampling techniques, to pursue the identification of new biochemical

markers in the premotor stage of Parkinson's disease in the future.


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Prerequisites to launch neuroprotective trials in Parkinson's disease: An

industry perspective

Authors: Johannes R. Streffer, Igor D. Grachev, Cheryl Fitzer-Attas, Baltazar Gomez-

Mancilla, Babak Boroojerdi, Juliana Bronzova, Susanne Ostrowitzki, Stephen J. Victor,

Paulo Fontoura, Robert Alexander

Realizing that 60% to 80% of dopaminergic nigrostriatal neurons are nonfunctional at the

time of clinical diagnosis, there is an emerging consensus that disease-modifyingtreatments should be initiated in the earliest stages of Parkinson's disease (PD). To date,

clinical trial designs and metrics in PD have been focused on motor symptoms as the core

feature of the clinical disease. To identify earlier or pre-motor populations in PD, newmarkers have been proposed. We address the prerequisites needed to use these pre-motor

markers in clinical trials for the selection of subjects, definition of populations, and

monitoring of disease progression. This may require the development of new diagnosticcriteria potentially based on non-motor clinical signs, imaging techniques, or biological

features, all requiring discussion in a regulatory framework. Questions addressed include:Which steps must be taken to gain a broad consensus in the field from academic opinion

leaders, patient advocacy groups, regulatory bodies, and industry? How do we preventthe selection of subgroups, which may not be representative of the full disease spectrum?

Is there a way forward in personalized medicine? How do we balance risk and benefit in

an at-risk population? While many tools are available, a concerted effort is required todevelop integrated data sets, as well as to achieve the necessary standardization for

multicenter clinical trials. To this end, public-private consortia (including academic

centers, patient advocacy groups, and industry) will be of crucial importance toprospectively investigate and define the best tools and treatment paradigms.

Defining at-risk populations for Parkinson's disease: Lessons fromongoing studies

Authors: Daniela Berg, Ken Marek, George W. Ross, Werner Poewe

It is currently widely acknowledged that the natural history of PD includes a preclinical

phase, and there are increasing efforts to identify markers that would allow the

identification of individuals at risk for PD. Here, we discuss the issues related to definingat-risk populations for PD and review findings of current population-based cohorts that

have reported potential biomarkers for PD, such as the Honolulu-Asia Aging Study

(HAAS) and the PRIPS (Prospective Validation of Risk factors for the development ofParkinson Syndromes) study. We also discuss enriched risk cohorts designed to evaluatespecificity and predictive value of markers exemplified by the PARS (Parkinson

Associated Risk Study) and the TREND (Tbinger evaluation of Risk factors for the

Early detection of NeuroDegeneration) study. Although there is still a long way to go,studies designed according to these concepts might eventually provide sufficient data to


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form the basis for future screening programs for PD risk to be applied at a population

level.

The significance of defining preclinical or prodromal Parkinson'sdisease

Authors: C. Warren Olanow and Jos A. Obeso

A body of clinical and pathologic evidence supports the concept that there a pre-Parkinson state exists prior to the time when Parkinson's disease (PD) can be formally

diagnosed. The ability to define the preclinical or prodromal PD state has many important

implications. First, understanding the timing and sequence of pathologic change thatoccurs in PD could provide important clues as to the etiology and pathogenesis of PD,

and provide insight into cell vulnerability factors. Second, defining a population of

patients with preclinical PD would provide a potentially important group of subjects forclinical trials attempting to define disease-modifying therapies. And, finally, being able to

determine that a person has PD at an earlier time point than is currently possible would

permit the introduction of a putative disease-modifying therapy at a time when it could

have more profound and long-lasting effects. This paper reviews the clinical significanceof defining preclinical PD.

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HOST: This concludes this months podcast of the MovementDisorders Journal, April

2012 Special Issue. Thank you for listening and we hope you will join us again next

month.

Podcast Script April Special 2012 v1

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