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At the conclusion of the activity, participants should be able to:

1. Describe the clinical presentation, management, and progression of Parkinson’s and other movement disorders

2. Summarize the rationale of rehabilitative approaches in people Learning with Parkinson’s disease and other movement disorders Psychological Issues in Parkinson’s 3. Identify the key areas of rehabilitation in people with Parkinson’s Objectives disease and other movement disorders Disease and Movement Disorders 4. Describe the reasoning behind designing and modifying a patient- specific treatment plan Priya Jagota, MD 5. Identify strategies for collaborating with physicians and other health professionals

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Parkinson’s Disease

Conflict of Interest

Nothing to disclose

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Depression

Anxiety

Apathy - Lack of motivation Psychological Issues in PD Psychosis • • • Delusion Impulse Control Disorders

• Ref: Anna Sauerbier et al., 2017 5 7

• Clinical manifestations of in PD

• Depressed mood, decreased interest and pleasure

• Anxiety and apathy may accompany

• May overlap with other symptoms of PD

• Motor symptoms - slowness or psychomotor retardation, blunted

affect

• Somatic symptoms -muscle tension, gastrointestinal problems Depression • Vegetative symptoms - changes in weight or appetite • Cognitive symptoms

• Less likely: excessive guilt; feelings of worthlessness, hopelessness, or

helplessness; delusions; or suicidality

Aarsland., 2012 8 9

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Neurobiology of depression in PD

• Limbic and orbitofrontal cortex • Disruption of dopamine, serotonin, and noredrenaline Anxiety

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Anxiety symptoms in PD Clinical Phenotypes Generalized Panic attacks Phobias Anxiety Disorders Predominantly Anxious- Predominantly Depressed Depressed Anxious Seen more in Higher impact on Prevalence 25-52% younger patients and with motor QoL than depression fluctuations

Ref: Anette Schrag and Raquel N. Taddei, 2017 Ref: Anette Schrag and Raquel N. Taddei, 2017 12 13

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Neurobiology of anxiety in PD

Decreased DA • Reduced DAT availability in caudate levels and L putamen

Decreased 5HT • Degeneration of raphe nucleus and Apathy and NE locus ceruleus Limbic • amygdala and hippocampus dysfunction

Weintraub et al.,2005 14 15

difficult to redirect attention to novel stimuli, manipulate complex external or “nothing to say” and internal information, or generate plans “nothing matters” to Apathy them

A state of • Decreased motivation • that manifests as a decrease in goal-directed behaviours, and • Apathy can be variably characterised by subdomains, neural substrates, reduced interests or and potential treatments • cannot be attributed to diminished level of , cognitive impairment, or emotional distress

Ref: Pagonabarraga J. et al, 2015 Ref: Pagonabarraga J. et al, 2015 16 17

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An 80-year-old woman presented with bilateral limb slowing and gait disturbance 2 years ago. PE revealed bilateral rigidity and bradykinesia with prominent axial rigidity. Dx: PSP with apathy 6 months ago she started having falls. Apathy along with other frontal lobe symptoms She has frequent urinary incontinence but no constipation. She never wanted to leave the house, speaks only when spoken to and is usually in bed most of the day. She is also unconcerned about her urination. She has groaning sometimes but there’s no obvious .

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Treatment of Depression, Anxiety, Apathy

• Target: Dopamine, Serotonin, Noradrenaline

Psychosis

SE=Strong Evidence Ref: Eva Schaeffer and Daniela Berg, 2017

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• Delusions are false, fixed, idiosyncratic beliefs that are maintained despite evidence to the contrary. What is • are abnormal without a physical that “Psychosis” can involve any sensory modality and may be simple or complex in form. in Parkinson’s disease? • Presence hallucinations consist of the experience that someone is present when nobody is actually there.

• are misperceptions of real stimuli that are often visual in nature.

Ravina B et al., 2007 23 24

Illusion Psychosis in PD Presence Hallucination – Clinical Manifestations Hallucination – all sensory domains

• Visual – most common – 90% (Psychosis • With insight – “Benign hallucination” • Auditory • • Tactile Without insight – “Malignant hallucination” Spectrum • Olfactory Symptoms) • Gustatory Delusion - paranoid, consisting of beliefs about spousal infidelity or abandonment

Ravina B et al., 2007 Dominic H. ffytche et al., Dominic H. ffytche et al., Natures Review Neurology Natures Review Neurology 2017 2017 25 27

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Minor Hallucination:

Well-formed • visual illusions • Presence and passage (fleeting, vague images in the peripheral vision) Visual People or animals Hallucination hallucinations Inanimate objects – less common in PD • Can occur up to 40% Reoccuring contents • Less likely to be disruptive and are,

• therefore, less likely to be spontaneously reported

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Auditory Hallucination in PD Case: PD for 10 years • indistinct whispers VH for 1 year 1 week – has been seeing • music someone and some • threatening voices voices that they will come and take her family away from her • variably co-occur with visual hallucinations (8%–13%) She would get a broom and hit • less likely to be seen in isolation “them”

Ravina B et al., 2007 30 35

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Case : A 63 year-old female with a 9-year history of Tactile, PD presented with visual and tactile hallucination. Olfactory • Uncommon and Gustatory • Generally seen with visual Hallucinations hallucinations in PD

• Ravina B et al., 2007

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Manifestations of Psychosis Risk/Associated Factors

• Older age • Advanced disease • Seconds to minutes • Female • Depression • Can occur many times per day • RBD • • Autonomic dysfunction Prevalence increases with disease stage • Severity of olfactory impairment • Usually occurs in the evening or at night first • AD pathology • Reduced higher visual function Other • – Dopamine agonist, MAOB-I, Levodopa • Anticholinergics Ravina B et al., Mov Disord 2007 Zhu K et al., Mov Disord 2013 Ffytche DH et al., JNNP 2017 39 41

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If acute, look for Minor hallucinations can occur in the premotor stage precipitating factors: • Metabolic Severity of the hallucination can Psychosis in Summary increase with disease progression • toxic encephalopathy PD • concurrent infection Increased risk of dementia, nursing • review medications - overdose, home placement, mortality search for polypharmacy, anticholinergics

Goetz CG, et al, Nature Review 2009 Rabey JM, PRD 2010 Ravina B, et al, Mov Disord 2007 44 45

Non-pharmacological Impulse Control and Related Disorders

• Environmental modification • Adequate lighting • Removing obscure things • Psychological treatment

Treatment Pharmacological • Quetiapine • • Pimavanserin

ECT

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Impulse Control and Related Disorders Impact

• Impulse Control Disorders (ICDs) • Compulsive gambling

• Compulsive buying

• Compulsive sexual behavior

• Compulsive eating

• Punding (stereotyped, repetitive, purposeless behaviors)

• Hobbyism (e.g., compulsive internet use, artistic endeavors, writing)

• Dopamine Dysregulation Syndrome (DDS – compulsive medication overuse)

52 Ref: Weintraub D. and Claassen D., 2017 51 52

Treatment

Reduce dopamine agonists first Other meds

Ref: Weintraub D. and Claassen D., 2017 55 57

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• Dystonia is a movement disorder characterized by sustained or intermittent muscle contractions causing abnormal, often Psychogical Issues repetitive, movements, postures, or both. Dystonic movements are typically patterned, in Dystonia Dystonia twisting, and may be tremulous. Dystonia is often initiated or worsened by voluntary action and associated with overflow muscle activation.

Ref: Albanese A., et al. Phenomenology and Classification of Dystonia: A Consensus Update, Mov Disord 2013 58 59

Psychogical Issues in Chorea

Ref: Macerollo A. and Martino D., 2016 Bradnam LV. et al., 2021 (Neurorehabilitation in dystonia: a holistic perspective) 61 62

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Genetics Genetic Causes of Adult-onset Chorea

•AD • Autosomal dominant • Autosomal recessive • •AR Huntington’s disease • HD-like-illnesses (3) Causes of • C9orf72 repeat expansions •X-linked • Neuroacanthocytosis Chorea • HD-like-illnesses (1,2,4) •Mitochodrial • Wilson’s disease • Spinocerebellar ataxias (1,2,3,17,DRPLA) • Primary familial calcification Acquired causes (Fahr’s syndrome) • X-linked recessive • Neuroferritinopathy (NBIA) • McLeod syndrome

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Vascular-related

• Stroke, Abnormal vasculatures

Metabolic

• Hyperglycemia, Hypoglycemia, Hypernatremia, Hyponatremia, ACQUIRED Hyperthyroidism Autoimmune

CAUSES OF • SLE, Antiphospholipid syndrome • Autoimmune paraneoplastic syndromes – anti-CRMP5, anti- ADULT-ONSET NMDA, anti-Hu, anti-Yo Huntington’s CHOREA Infection • AIDS (opportunistic infection), Neurocysticercosis, Toxoplasmosis Disease

Drug-induced

• Tardive dyskinesia • Dopaminergic drugs, anticonvulsants

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Triad Neuropsychiatric • Motor disorders - chorea Manifestations • Cognitive deficits of Movement Disorders in Clinical • Psychiatric symptoms – depression, Features high risk for suicide, anxiety Children • Other emotional disorders – irritability, apathy, personality changes

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Implications for Rehabilitation

Ref: Ben-Pazi H. et al., 2011 70 71

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Role of caregiver

Know your patients before you start

Well-lit, non-cluttered room

Medications – on-off period

Psychological and other non-motor issues

Motivation

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Thank you

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