Non-motor symptoms as a marker of. Michael Samuel

Transcription

1 Non-motor symptoms as a marker of progression in Parkinson s s disease Michael Samuel London, UK 1

2 Definitions and their problems Non-motor symptoms as a marker of progression Non-motor symptoms (NMS) (i.e. a complaint by a patient) t) are not signs detected by a neurologist, for example, Anosmia or Abnormal neuropsychometry results So what is the significance if these are present in an asymptomatic patient? What is meant by progression? Which NMS are most informative of progression? 2

3 Types of non-motor progression Three alternative options to assess progression 1. Individual NMS worsens from mild to severe, but not all NMS behave predictably, for example: Anosmia can be static with time REM sleep behaviour disorder (RBD) can resolve (or post-date PD) Mild cognitive impairment in PD can worsen into PD dementia 2. Qualitative: One NMS added to another Anosmia, then constipation, then depression 3. Quantitative: Overall NMS burden Is a total NMS score meaningful (compared with Unified PD Rating Scale [UPDRS III])? 3

4 How do we measure non-motor progression? Total NMS scale (NMSS) 1 score Except some NMS will get worse with treatment (visual hallucinations, sleep, hypersexuality), y), while others may improve and others are unaffected Severity Treatment 1 Chaudhuri et al. Mov Disord 2007;22: To view abstract, click Abstracts link above 4

5 Summary Measuring the progression of NMS requires multiple l approaches single domain items combined items multiple modalities (e.g. clinical and pathological) Progression of NMS is complex 5

6 Which NMS are most informative about early disease? Which h NMS are most informative about early disease? GPSRC CNS RTG 6

7 Pre (motor) clinical disease: types of study for identifying risk of PD Consider a symptom associated with PD (e.g. hyposmia, RBD, constipation, depression) Identify a population who have only that symptom without neurodegeneration (i.e. an idiopathic condition) Follow-up a large group of patients with only that symptom for a long time to see how many develop PD (or other neurodegenerations) by clinical examination for UK PD Society Brain Bank criteria by questionnaire i by phone by pathological examination 7

8 NMS in early (preclinical) PD anosmia 90% prevalence in PD, non-progressive 1 What is risk of developing PD if hyposmia exists? Ponsen et al. 2 prospective study of 361 asymptomatic first degree relatives of PD patients with 2-year follow-up: n=40 hyposmic + SPECT + clinical examination n=38 normosmic + SPECT + clinical examination n=283 normosmic + Parkinson s s questionnaire, positive in 10 who had clinical examination Outcome:10% of the 40 hyposmic patients with abnormal dopamine transporter levels developed clinical PD after 9 19 months; none of the other patients developed PD SPECT, single photon emission computed tomography. 1 Hawkes et al. J Neurol Neurosurg Psychiatry 1997;62:436 46; 2 Ponsen et al. Ann Neurol 2004;56: To view abstract, click Abstracts link above 8

9 NMS in early (preclinical) PD RBD 15 40% prevalence in PD What is risk of developing PD if RBD exists? Postuma et al. retrospective study 93 patients ts with idiopathic RBD confirmed by polysomnography og y (= time 0) 78 had examination in person for diagnosis of PD, Lewy Body Disease or Alzheimers disease; 9 had examination in person and phone call; 6 had diagnosis made on phone call only No neurodegeneration at entry Follow-up period mean 5.2 years Calculated 5- and 10-year risks from Kaplan Meier survival analysis (only definite clinical diagnoses included) 14 patients developed PD 5-year risk 18%; 10-year risk 41% Postuma et al. Neurology 2009;72: To view abstract, click Abstracts link above 9

10 NMS in early (preclinical) PD constipation Lewy pathology in myenteric plexus delayed bowel transit time Prevalence 28 80% Abbott et al. prospective study 6790 men recruited between in Honolulu heart programme Over 24-year follow-up, 96 developed d PD Risk of PD increased times if < 1 bowel motion/day compared with 1 2/day Abbott et al. Neurology 2001;58: To view abstract, click Abstracts link above 10

11 NMS that can be seen in early PD Mild cognitive impairment (MCI) Prospective multicentred Norwegian study Non-demented, drug-naive PD patients (n=196) at 28 months follow-up; healthy controls (n=201) MCI is defined as 1 cognitive domain > 1.5 SD below mean of an age-matched control group from same area What is prevalence of MCI in PD? 19% of PD patients had MCI by this definition 1/3 had cognitive decline in memory domain 2/3 had cognitive decline outside memory domain Relative risk of MCI in untreated early PD is 2.6 if aged > 65 years and 1.5 if aged < 65 years, compared with healthy controls Aarsland et al. Neurology 2009;72: To view abstract, click Abstracts link above 11

12 MCI and rate of progression to dementia Janvin et al. prospective study of 72 PD patients recruited in 1997, none with dementia PD patients with MCI (n=38) 16% single amnestic 45% single non-amnestic 39% multiple amnesic 62% had dementia at 4 years Cognitively intact healthy controls (n=34) 20% had dementia at 4 years Janvin et al. Mov Disord 2006;21: To view abstract, click Abstracts link above 12

13 Markers of late stage PD Postural hypotension: prevalence 30% With MSA (n = 15) took 24 months to develop With PD (n = 11) took 166 months to develop Bladder dysfunction With MSA took 12 months to develop With PD took 144 months to develop MSA, multiple system atrophy Wenning et al. J Neurol Neurosurg Psychiatry 1999;67: To view abstract, click Abstracts link above 13

14 NMS possibly related to progression of motor signs Drooling of saliva Off pain/dystonia Insomnia (nocturnal off) Dysphagia Non-motor symptoms that can be unrelated to disease progression... and possibly related to treatment and/or social items Pain Excessive sleepiness Impulse control disorders Impaired sexual function 14

15 Conclusions 1. NMS as a marker of progression is a complex topic 2. NMS can be related to the disease and to the treatment 3. NMS need to be assessed individually and pooled 4. Some NMS can be anticipated, minimized and treated 5. Disease progression should not prevent managing NMS appropriately 15

16 Question 1. In patients with idiopathic RBD, what is their risk of developing PD after 10 years? A) 21% B) 31% C) 41% Correct - Click anywhere to continue Incorrect, please try again Incorrect, You must please answer try again the question before continuing Submit Clear 16

17 Question 2. In the study by Janvin et al, how many times more likely were patients with PD and MCI to develop dementia than cognitively i intact, healthy h controls? A) ~ Twice as likely B) ~ Three times as likely C) ~ Four times as likely Correct - Click anywhere to continue Incorrect, please try again Incorrect, You must please answer try again the question before continuing Submit Clear 17