premotor pd: autonomic failure2/5/2015 3 premotor pd: autonomic failure prof. gregor k. wenning...

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Premotor PD: autonomic failure Prof. Gregor K. Wenning

Premotor PD: autonomic failure

Prof. Gregor K. Wenning

Division of Neurobiology

Department of Neurology

Medical University of Innsbruck


Non-motor symptoms in PD

• Autonomic• OH, constipation, impotence, urinary incontinence or retention, hyperhidrosis

• Hyposmia

• Sleep

• Cognitive deficits• Executive dysfunction, MCI, dementia

• Psychiatric deficits• Depression, psychosis, anxiety, apathy

• Other• pain


Lim & Lang 2009

NMS in PDExtranigral pathology

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ILBD: PANS InvolvementBloch et al. 2006


2004

ThSG

ThSG

FrontCtx

SNpc

CingulCtx

SNpc

Autonomic failure in premotor PD


Premotor PD: Cardiovascular dysfunction

1. Orthostatic hypotension (OH)

2. Chronotropic insufficiency

3. Heart rate variability

4. Cardiac sympathetic imaging

Palma & Kaufmann 2014

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Orthostatic hypotension- Consensus criteria (Freeman et al 2011) -

1. Abnormal blood pressure drop (∆ 20/10)within 3 minutes of standing or tilt

2. Abnormal blood pressure drop (∆ 20/10)after 3 minutes of standing or tilt = delayed OH


OH SymptomsCerebral hypoperfusion:

• Light-headedness

• Dizziness

• Visual disturbances

• Loss of consciousness

• Impaired cognition

Muscle hypoperfusion:

• Coat-hanger ache

• Gluteal ache

• Calf ache

Renal hypoperfusion:

• Oliguria

Non-specific:

• Fatigue

Modified from Mathias 1999


2003

2006

14% (7 / 51)

Early 60% (21 / 35) Premotor 11% (4 / 35)

Early / premotor PD-OH

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Prodromal autonomic features in PD & DLBPostuma et al 2013

Systolic drop, erectile

dysfunction, and

constipation could

identify disease up to 5

years before diagnosis

with sensitivity ranging

from 50% to 90%.


• Prospective cohort study• 14-year follow-up

• > 5000 adults aged ≥ 65 years• Premotor OH in 18% of 214 incident PD cases

• OH in 18% of non-PD controls

No evidence of premotor OH

MDJ 2012

Premotor OH


Chronotropic insufficiencyMDJ 2013MDJ 2013

Retrospective cohort study2539 patients without neurological diseaseCardiac stress testing at baseline18 incident PD cases within 4 yearsBlunted heart rate compared to non-PD cohort

Chronotropic insufficiency: a sign of cardiacsympathetic denervation?

Chronotropic insufficiency

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Heart rate variability

1. HRV parameters are reduced in PD and iRBD (Valappil 2010, Palma

2013)

2. BUT Prospective studies failed to prove a predictive value (Postuma

2010, Jain 2012, Palma 2013)

? number of incident PD too small? only linear HRV parameters used


Cardiac sympathetic denervation- Kashihara 2006, Orimo 2008 -

MDJ 2012PDHCMSA


Cardiac sympathetic denervationidentifies premotor PD ?

MDJ 2013

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Constipation: a strong PD risk factor


Premotor sexual dysfunction


50 patients, 66 yrs, DD 2 yrs, HY 1.9Urinary storage symptoms 64%, voiding symptoms 28%Urodynamics: detrusor overactivity 58%, underactivity 50%Few patients with urge incontinenceNo sphincter EMG abnormalities

No correlation with gender, disease severity or motor type

Urinary biomarkers?

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Feature MSA PAF PD

Site Preganglionic Postganglionic Postganglionic

Prognosis Poor Survival > 10-20 yrs Prolonged survival

Motor features Always Rare Always

Neuropath Marker GCI LBs LBs

OH Common Common Less common

Sleep apnea Common Uncommon Common

Urinary dysfunction Early Late Intermediate

Supine NE Normal Very low Intermediate

Orthostatic NE rise Subnormal Subnormal Intermediate

Postsynapticadrenoreceptor

supersensitivity

Mildly increased Increased Mildly increased

Garland et al 2013

PAF among the primary autonomic failure syndromes


Conclusions

• Autonomic failure is an early feature of PD

• No single autonomic feature accurately predicts PD

• Low specificity of some autonomic features

• Identification of autonomic features to be improved

• No premotor data for some autonomic features such as sweating disorder


Division of NeurobiologyDepartment of Neurology

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Acknowledgements

premotor pd: autonomic failure2/5/2015 3 premotor pd: autonomic failure prof. gregor k. wenning...

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