Rehabilitation Management of Parkinsons Disease

1. Rehabilitation Management of Parkinsons Disease Susan Stickevers, MD Residency Program Director & Assistant Clinical Professor, SUNY Stony Brook Dept of PM&R

2. Parkinsons Disease • Is a chronic, progressive neurodegenerative disorder with a multifactorial etiology. • It is superseded only by Alzheimer’s Disease as the most common neurodegenerative disorder

3. Demographics of Parkinsons Disease • Prevalence of 0.3 % in the US population • 1 – 2% of all persons > 65 yrs old • 4 – 5% of all persons > 85 yrs old • In US : > 1 million have diagnosis of Parkinsons – this is greater than the combined number of MS, ALS, and muscular dystrophy patients added together • Usual age at onset – early 60s • 10% of all those affected are < 45 yrs old – referred to as young onset Parkinsons • 40, 000 new cases of PD will diagnosed this year • Lifetime risk of Parkinsons for men : 2.0% • Lifetime risk for women : 1.3% • Incidence of the disease is lower in African Americans than in Caucasians in the USA

4. An Interesting Fact • The Chinese have the lowest rates of Parkinsons Disease • It has been suggested by Fahn & Jankovic that this is may be due to consumption of large amounts of green tea by the Chinese which contains antioxidants

5. Etiology • Parkinsonian symptoms can arise from either the neuropathological condition PD (idiopathic PD) or other forms of Parkinsonism • For neuropathological PD, 90% of cases are sporadic • 10% are of genetic origin – 6 different gene mutations have been identified – the Parkin genes • Genetic forms of PD are seen more frequently in young onset PD • A combination of environmental factors or toxins, genetic susceptibility, and the aging process may account for many of the sporadic cases

6. Secondary Parkinsons • Can be caused by : • Medications – antipsychotics & antiemetics, lithium, reserpine, aldomet • Sequelae of CNS infection – Prion Diseases, Jakob Creuzfeldt, SSPE, HIV, post encephalitic • Toxin Exposure – Manganese, Rotenone, Paraquat • Vascular Metabolic Disorders – Binswanger’s Disease • Drug Induced – MPTP – byproduct of Ecstasy production • Certain neurodegenerative conditions may exhibit also exhibit Parkinsonian features, these are called the Parkinsons Plus Syndromes – included in this category are progressive supranuclear palsy, MSA, Lewy Body Dementia and CBD • Trauma – Pugilistic encephalopathy

7. Risk Factors for Parkinsons Disease • The most important risk factor for Parkinsons is advancing age. • Other environmental or lifestyle risk factors associated with Parkinsons include : • Rural living • Exposure to herbicides & pesticides – exposure to the synthetic pesticide paraquat is associated with Parkinsons (organic pesticides are not necessarily safe - rotenone or Derris Dust exposure can induce Parkinsonism) • Drinking well water • Working with solvents – in particular – hexane • Manganese toxicity – sometimes seen in welders, or patients exposed to incorrectly prepared TPN solutions

8. Idiopathic Parkinsonism • Most common form of Parkinsonism : • Idiopathic form first described by James Parkinson, A British surgeon & paleontologist in 1817 in his “Essay on the Shaking Palsy”

9. Pathophysiology of Idiopathic Parkinsons • Pathological hallmark of PD : degeneration of dopaminergic neurons in the substantia nigra compacta, resulting in depletion of striatal dopamine • This neurotransmitter regulates excitatory & inhibitory outflow from the basal ganglia • Some of the dopaminergic neurons survive, and these are found to contain Lewy Bodies

10. Pathophysiology of Parkinsons • Lewy Bodies are eosinophilic intracytoplasmic inclusions, composed of numerous proteins • Protein accumulation plays a prominent role in the pathogenesis of both sporadic & familial forms of PD • Lewy bodies may actually be cytoprotective

11. Lewy Bodies • The neurodegenerative process in PD is not limited to the substantia nigra compacta • Neuronal loss also happens in other brain regions, which accounts for the motor & non motor features of the disease

12. Parkinsons Disease – The Six Cardinal Features • Tremor at rest • Rigidity • Bradykinesia • Loss of postural reflexes • Flexed Posture • Freezing (Motor Block) • Diagnostic Criteria : Definite Parkinsons : at least two of these features must be present, one of them being # 1 or # 2 • Probable : Feature # 1 or feature # 2 is present • Possible : at least two of features # 3 – 6 must be present

13. Diagnostic Testing • There are no clinical tests widely available to definitively make the diagnosis, however, if confirmation of the clinical diagnosis is desired, order serial 6 – fluoro L dopa PET scans which will demonstrate a gradual decline in uptake in the putamen & caudate in the Parkinsons patient • Alternative Imaging Study - Serial Beta CIT SPECT imaging revealing gradual loss of function in the striatum • On the right, see the PET scan of a patient who underwent implantation of fetal tissue into the right putamen - note the recovery of function in the right putamen and the progressive loss of function in the left putamen

14. Typical MRI Appearance in Parkinsons Disease • Standard MRI studies in Parkinsons are normal • If warranted, consider High Field Strength 1.5 Tesla T2 weighted Brain MRI • Typical Appearance in Parkinsons : wider area of lucency will be noted in the subthalamic nucleus that is probably indicative of increased accumulation of iron – iron deposition occurs when there is a loss of connectivity to the cortex

15. Early Non - Specific Signs of Parkinsons • Generalized stiffness • Pain or Paresthesias of the limbs – in particular, shoulder pain • Constipation • Low Uric Acid Levels • Sleeplessness • Reduction in volume of the voice • Loss of sense of smell • Seborrheic Dermatitis – see photo on the right • These symptoms precede onset of the motor symptoms of Parkinsons • A Retrospective Study of Early Symptoms of Parkinsons Disease, Przuntek, 1992)

16. Early Signs of Parkinsonism • Problems with fine motor skills • Decreased sense of smell • Loss of appetite • Tremor occurring with anxiety • Decreased arm swing on one side – a principal finding in Parkinsons is asymmetry in neurological findings • Decreased emotional expression • Personality changes, especially introversion & inflexibility

17. Parkinsonism is Frequently Misdiagnosed • Clinical presentation may vary from patient to patient • It is not uncommon for PD symptoms to go unrecognized or unreported for years

18. Two Major Forms of Parkinsonism • Tremor Dominant – has a better prognosis • PIGD – Postural Instability & Gait Dysfunction Variant – has a poorer prognosis

19. The Cardinal Features : Bradykinesia • Bradykinesia manifests itself as : • Slow reaction times • Impaired fine motor coordination that interferes with ADL • Drooling due to failure to swallow saliva • Monotonic & hypophonic dysarthria : due to incoordination of the muscles of vocalization • Loss of facial expression (hypomimia) – leads to mask facies & decreased blink rate • Reduced armswing when walking • Micrographia – small cramped handwriting • Bradyphrenia – slowness of thought • The extreme form ofbradykinesia is akinesia : the inability to initiate movement • Bradykinesia is the most disabling feature of Parkinsonism. • With a sudden surge in emotional energy, the bradykinetic patient may be able to catch a ball or make a fast movement • This phenomenon is called kinesia paradoxica

20. Pathophysiology of Bradykinesia • Thought to result from failure of basal ganglia output to reinforce the cortical mechanisms that prepare & execute the commands to move • Reduced dopaminergic function disrupts normal motor cortex activity • Secondary factors which contribute to bradykinesia include muscle weakness, tremor, and rigidity • Bradykinesia results from excessive activity in the subthalamic nucleus and the internal segment of the globus pallidus

21. The Cardinal Symptoms : Tremor • Resting tremor may be considered to be the most typical sign of Parkinsons • A common initial symptom of the disease is an asymmetrical resting tremor – seen in 70 – 90% of patients at presentation • Asymmetrical resting tremor usually involves the thumb or wrist • If resting tremor is not present, consider that the patient’s Parkinsonian symptoms are caused by a disorder other than PD • The typical resting tremor has a frequency between 4 – 6 Hz • Tremor is most prominent in the distal part of an extremity – in the hand, called a pill rolling tremor • Pill rolling tremor involves the forefinger & thumb at a frequency of 3 -6 cycles per second is the classical presentation of tremor • When tremor is present in the head, it occurs in the region of the lips, chin and jaw – only occasionally in the neck • **Tremor is more likely to be the presenting symptom in young patients, whereas older patients have more prominent bradykinesia**

22. Treatment of Tremor • Anticholinergics are effective in treatment of resting tremor • Usually used in younger patients ( < 60 yrs) with intact cognition & predominant tremor • Benztropine • Trihexyphenidyl • Side Effects : constipation, blurry vision, urinary retention, confusion, hallucinations

23. Prognostic Significance of Tremor • Presentation with tremor as the initial symptom often confers a positive prognosis – slower progression • There is a subset of patients with Parkinsons who have “benign tremulous parkinsonism” – these patients have : • A family history of tremor • Minimal progression of the disease process • Poor response to levodopa

24. Rigidity & Flexed Posture • Rigidity is manifested by increased resistance throughout the range of motion • Rigidity can manifest itself proximally – in the neck, shoulders, and hips • Gait in Parkinsons is characterized as : • Short & shuffling steps • Stooped posture • Narrow base of support • Flexed knees

25. The Cardinal Signs : Flexed Posture - Camptocormia • Patient on the left had camptocormia due to unrecognized, untreated Parkinsonism • The picture on the right depicts his response to a single test dose of Sinemet. • Camptocormia is a postural deformity seen in the Parkinsons patient • This manifestation of Parkinsonism is often dismissed by physicians as hysteria

26. The Cardinal Signs – Freezing • Freezing is also known as motor block • Most often affects the legs when walking, but it can also affect the arms and eyelids • Freezing consists of a sudden, transient inability to move • It typically causes hesitation when initiating walking & sudden inability to move feet when turning or walking thru narrow passages – such as doors or elevators – or when patients are about to reach a target destination • Freezing is thought to related to noradrenergic deficiency related to degeneration of the locus coeruleus

27. The Use of Gestes Antagonistes to Overcome Freezing • Patients learn (or may be taught) a variety of tricks (French : gestes antagonistes) to overcome freezing attacks, such as : • Marching to command (left, right,left, right) • Stepping over objects, such as a crack in the pavement, the end of a walking stick • Walking to music or a metronome • Shifting body weight • Rocking movements trunk • Train your patient to perform gestes antagonistes !!!

28. Association of Freezing with the Parkinsons Plus Syndromes • When freezing occurs early in the disease process, (< 3 yrs.) or early postural instability (< 3yrs) is present, or is a predominant symptom : • Consider that your patient may have a Parkinsons Plus Syndrome – not Parkinsons - such as • PSP • MSA • Vascular Parkinsons

29. Non Motor Features of Parkinsons • The clinical course of Parkinsons is not limited to motor symptoms • Non motor symptoms & disorders significantly affect the health related quality of life (HRQOL) • Surveys of PD patients reveal that approximately 90% have at least 1 non motor symptom • 10% of PD patient have 5 non motor symptoms • The non motor symptoms contribute to shortened life expectancy

30. Common Non - Motor Features of Parkinsons • Neuropsychiatric • Impulse Control Disorders • Sleep Disorders • Autonomic Dysfunction – orthostatic hypotension, hyperhidrosis, hypohidrosis, sexual impotence can be seen in Parkinsons – but if these features are noted early in disease process, your patient may have MSA • Sensory Symptoms – paresthesias, oral & genital pain are common – as is olfactory dysfunction • Other – Fatigue, Seborrhea, Diplopia, Blurred Vision, Weight Loss

31. Neuropsychiatric Disorders in Parkinsons Disease • Depression • Anxiety, including panic attacks • Cognitive Dysfunction • Dementia • Psychosis • Confusion or delirium • Apathy

32. Depression in Parkinsons • Most common neuropsychiatric disorder in PD patients, affecting up to 50% • Depression is often comorbid with anxiety disorder • Can be observed at any stage of the illness – including prior to onset of motor symptoms • Depression is associated with increased disability, poor HRQOL, and a more rapid progression of motor impairment • It is unclear whether or not the depression is reactive or related to neuropathology • Most patients with Parkinsons who are depressed are not treated or treated inadequately for depression – resulting in increased disability • Weintraub et al, J. of Geriatric Psychiatry & Neurology, 2003 • Routine screening for depression & anxiety with a validated instrument is recommended • Validated Instruments : Beck Depression Inventory, Geriatric Depression Screen, Hamilton Depression Inventory, Beck Anxiety Inventory, Speilberger State Trait Anxiety Inventory

33. Risk Factors for Depression in the Parkinsonian Patient • Increasing severity of cognitive impairment • Female gender • Early onset disease • Personal history of depression prior to onset of disease

34. Treatment of Depression – Evidence Based Medicine • Meta – Analysis : Fewer than 30 studies exist in the literature which evaluate the effectiveness of antidepressants in PD • The AAN recommends the use of amitriptyline for the treatment of depression in PD based on their review of available studies • TCAs may not be well tolerated by all Parkinsons patients due to the side effect profile – particularly the orthostasis & worsening cognition

35. Most Frequently Used Antidepressants in Parkinsons • SSRIs are the most commonly used antidepressants • Well tolerated by the major of patients • This class of drugs do not appear to worsen motor symptoms in PD • In open label clinical trials, most PD patients did not experience side effects with maximal dosages • **Citalopram, escitalopram, and sertraline are recommended** - less prone to drug – drug interactions than paroxetine or fluoxetine

36. Antidepressant Doses

37. Anxiety in Parkinson Patients • Avoid benzodiazepines as these increase the risk to fall • Consider the use of an antidepressant which is also effective against anxiety • Escitalopram is a good choice of an antidepressant which can also act as an anxiolytic • Buspirone is well tolerated but has not been formally tested for its effectiveness in PD patients

38. Cognitive Dysfunction & Dementia in PD • Prevalence of dementia : 20 – 40% of PD patients : Six times higher than in the general population • Characterized by : • Psychomotor slowing • Impaired executive function • Inattention • Impaired visuospatial abilities • Memory impairment – due to poor retrieval of information in PD – as opposed to poor encoding of new information seen in Alzheimers Disease • Verbal cueing may aide recall in Parkinsons patients – this is not usually helpful in Alzheimers

39. Neurobiology of Development of Dementia in PD • Neurotransmitter deficits are responsible : • Decreased levels of the following are observed in PD : • Acetylcholine • Dopamine • Serotonin • Norepinephrine • Cholinergic & dopaminergic deficits have been linked to memory dysfunction & dysexecutive syndrome • Noradrenergic deficits have been linked to inattention • **Consider neuropsychological testing on all your PD patients at regular intervals**

40. Recommended Screening Tools for Dementia in the Parkinsons Patient • Cambridge Cognitive Examination • Folstein Mini Mental Status Exam • Montreal Cognitive Assessment – highly effective in detecting early cognitive changes • Hopkins Verbal Learning Test – assesses verbal memory abilities & recognition recall • Clock Drawing Test – useful to asses visuospatial & executive abilities

41. Comparison of the Clinical Features of Lewy Body Dementia, Parkinsons Dementia, & Alzheimers Disease

42. Risk Factors for Development of Dementia in Parkinsons Patients • Old age • Older age at onset • Increased severity of PD • Depression • Psychosis • Early executive impairment • Early memory deficits

43. Is it Lewy Body Dementia or Parkinsons? • The presence of dementia & psychosis early in the disease course is highly uncharacteristic of PD and favors a diagnosis of Lewy Body dementia

44. Treatment of Dementia in Parkinsons • Rivastigmine (Exelon) was found to be moderately effective in Parkinsons dementia in a large placebo controlled study & has received FDA approval for this indication • In small studies, the anticholinesterase donepezil in PD patients with dementia • Very rarely do these medications cause a worsening of Parkinsonian symptoms

45. Drugs for Cognitive Dysfunction in Parkinsons Disease

46. Impulse Control Disorders (ICD) • Impulse control disorders are defined as failure to resist an impulse, drive, or temptation to perform an act that is harmful to the person or others • Manifestations include compulsive gambling, hypersexuality, shopping, and binge eating. • ICD occurs at a frequency of 1.5% of the general population • In Parkinson Disease, one large scale study suggests that ICD affects 10 – 15% of patients with PD

47. Etiology of ICD in Parkinsons • Primary Etiology of ICD in Parkinsons – dopamine agonist therapy • No one agent has been identified to be more likely than another to induce ICD • Higher doses predict a greater risk for ICD • A history of ICD before onset of Parkinsons is a risk factor for exacerbation of this syndrome after initiation of dopamine agonist therapy • When prescribing dopaminergic agonist therapy, patients must be warned about the potential for developing an ICD • Screen patients on dopaminergic agonists for an ICD with the Minnesota Impulse Disorders Interview

48. Treatment of ICDs in Parkinsons • When ICDs develop in the Parkinsons patient, consider : • Dose reduction • Discontinuing dopaminergic agonist • Switching to another dopaminergic agonist • Consider a trial of an SSRI • Consider a trial of an atypical antipsychotic

49. Sleep Disturbance in Parkinsons • Some patients remain awake 30 – 40% of the night • Sleep dysfunction is manifested as : • Parasomnias • Nocturnal Insomnia • Difficulty initiating or maintaining sleep • Daytime Hypersomnolence

50. Etiologies of Sleep Disturbance in Parkinsons • Nocturia • “Wearing off” motor disability • Sleep Apnea – due to rigidity in phargyneal & respiratory musculature & neuropathological changes • Periodic Leg Movements • Restless Leg Syndrome – occurs in 20% of Parkinsons patients • Depression / Anxiety • Neuropathological Changes – degeneration of the brainstem nuclei involved in respiration • Medication related – for example, selegiline has amphetamine derative metabolites