Does this patient have Parkinsonism? Salvador Cruz-Flores, MD, MPH, FCCM Professor and Founding Chair Department of Neurology

Transcription

1 Does this patient have Parkinsonism? Salvador Cruz-Flores, MD, MPH, FCCM Professor and Founding Chair Department of Neurology

2 Nothing to disclose

3 Case Scenarios Context The Evidence o Populations o Prior Probability o Reference Standard o Test Characteristics Overview

4 Case 1 70-year-old man with 3-month history of progressive tremor and difficulty writing letters Physical examination Bilateral tremor, otherwise well. Continues to play golf

5 Case 2 68-year-old man with three-month history of right arm tremor and trouble getting up from chair Physical examination: Rigidity, Small steps, limited arm swing and limited facial expression

6 Questions What is the likelihood that these patients have Parkinson disease? Are there other elements of history or physical examination that would help you assess the likelihood of Parkinsonism?

7 Prior Probability Parkinson disease prevalence Aged 65+ years: 1% Aged 85+ years: 2% In older patients presenting with general neurological complaints the prior probability is likely higher

8 Why Do Clinical Evaluation? Diagnosis of Parkinson disease relies on serial clinical assessments No simple tested imaging or markers available Symptoms overlap other conditions o Supranuclear palsy o Multisystem atrophy o Dementia with Lewy bodies

9 Reference Standard Pragmatic standard: Serial clinical examinations performed by a specialist with or without concomitant treatment Neuropathologic standard: Depletion of brain stem pigmented neurons and proliferation of Lewy bodies

10 Pathophysiology Parkinson disease o Primary or idiopathic o Neurons and dopamine lost from substantia nigra and Lewy bodies Parkinsonism o 2 or more features present: tremor, rigidity, bradykinesia o Causes include viral, toxins, heredity, head trauma, hydrocephalus, or medications

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12 Step one Cardinal features of Parkinsonism Bradykinesia Rigidity Tremor Postural instability Diagnostic? o Reponse to L dopa

13 Bradykinesia in Parkinson disease Slowing of active movement or slowness in initiating movement Postural instability o Presents as changes in gait and balance o Short, shuffling steps o Loss of arm movement o Loss of postural reflex mechanisms leads to falls

14 How to Elicit Signs Bradykinesia Definition of Bradykinesia A decrease in speed and amplitude of complex movements Four maneuvers to consider o Tapping fingers o Twiddling o Pinching and circling o Tapping with the heel

15 Detecting Bradykinesia

16 Detecting Bradykinesia

17 Rigidity in Parkinson disease Involuntary stiffness of skeletal muscles Cog wheeling o Jerky motion of limbs as constant force is applied across a joint o Similar to ratcheting of clicking cogs or gears Spasticity (not usually present) o Selective increase in tone of flexor muscles in arms and extensor muscles in legs o Suggests diagnosis other than Parkinson

18 How to Elicit Signs Rigidity Examiner places thumb across patient s antecubital fossa to palpate the distal biceps tendon while passively moving the forearm ocog-wheeling rigidity: Intermittent, resistance alternates with relaxation olead-pipe rigidity: Smooth increase tone

19 Differential Diagnosis of Tremor Three common tremor syndromes otremor of Parkinson oclassic essential tremor ophysiologic tremor

20 Classification of Tremors Rest tremor Occurs in a body part not voluntarily activated and supported completely against gravity Action tremor Postural: Occurs while voluntarily maintaining a position against gravity Kinetic Occurs during any voluntary movement: simple, intention, task-specific, isometric

21 Kinetic Tremors Simple: Occurs during voluntary nontarget-directed movement Intention: Amplitude increases during visually guided movement (eg, finger to nose) Task-specific: Appears or is exaggerated by specific tasks (eg, writing) Isometric: Occurs during voluntary muscle contraction against a rigid stationary object (eg, squeezing hand)

22 Common Tremor Syndromes Tremor of Parkinson Slow frequency (4-6/second) Occurs at rest Inhibited during movement and sleep Aggravated by emotional stress Pill-rolling quality

23 The tremor of Parkinson disease 75% of patients complain of initial tremor at rest Usually starts upper extremity Appears intermittently Disappears during sleep Increases with stress or anxiety Signs typically begin unilaterally then progress asymmetrically

24 Common Tremor Syndromes Classic essential tremor Bilateral Usually symmetric postural or kinetic Family history common Tremor attenuated with alcohol

25 Common Tremor Syndromes Physiologic tremor High frequency (8-12/second) Differing degrees in different subjects Enhanced form is easily visible Postural (while maintaining a position against gravity) No evidence underlying neurologic disease Cause may be reversible (eg, caffeine)

26 Definition: How to Elicit Signs Tremor Rhythmical, involuntary, oscillatory movement of body part Observe with hands on lap o Rest or action o Frequency o Symmetry

27 Step two Red flags Pattern and distribution Course Medication response Tremor Myoclonus Dysphagia/dysarthria Dystonia Pyramidal signs Ataxia Gait and balance Polyneuropathy Eye movements Autonomic dysfunction Cognitive dysfunction Sleep disturbances

28 Step three Differential diagnosis

29 Step three Differential diagnosis

30 Step three Differential diagnosis

31 Patients Without Tremor Multisystem atrophy: Asymmetric rigidity, akinesia, autonomic dysfunction, cerebellar symptoms, and possible transient response to levodopa, but minority have tremor Progressive supranuclear palsy: Rigidity and postural instability but rare tremor Lewy body disease: Cognitive impairment is present at the onset with behavioral changes, hallucinations

32 Presentation Early Parkinson disease symptoms o Nonspecific symptoms o Generalized malaise and easy fatigability o Subtle personality changes o May occur years before tremor Next stage Symptoms frequently unilateral asymmetric o Tremor o Limb rigidity and bradykinesia o Postural instability

33 Secondary manifestations Disordered sleep (42%) Constipation (50%) Pain (50%) Depression (40%) Dementia (20%)

34 Prevalence Prior Probability o per population More common with age 1% of persons age > 65 2% of persons age > 85 Prevalence among older people with neurologic symptoms is higher but precise figures unavailable

35 Test Characteristics Sensitivity o SnN( )out: Negative tends to rule out Specificity o SpP(+)in: Positive tends to rule in

36 Test Characteristics Likelihood ratio (LR) o Determined for a particular test result o Conceptually related to how much more (LR > 1) or less (LR < 1) likely the disease is, given a particular test result o LR = 1 will not change your assessment of the likelihood of disease, given a particular test result

37 Using Likelihood Ratios Values of Likelihood Ratio: How much do they affect probability of disease? o LR = 1 o LR = 3-10 o LR = olr > 10 olr < 0.10 No effect on likelihood Disease More Likely Disease Less Likely Disease More Likely Disease Less Likely

38 LR: Impact on Likelihood of Disease 0 LR = 0.01 More Impact LR = 0.1 More Impact LR = 0.2 LR = 5 More Impact LR = 0.3 More Impact Increasing impact LR = 1 No Impact LR = 3 More Impact More Impact LR = 10 More Impact increasing impact LR = 100 More Impact

39 Useful Symptoms Findings (No. of Studies) LR+ LR History of shuffling gait (2) History of bradykinesia and difficulty rising from a chair (2) History of loss of balance (2) History of tremor (4) History of rigidity (3)

40 Useful Signs Findings LR+ (95% CI) LR (95% CI) Rigidity and bradykinesia 4.5 ( ) 0.12 ( ) Glabella tap 4.5 ( ) 0.13 ( ) Difficulty walking heel 2.9 ( ) 0.32 ( ) to toe Rigidity 2.8 ( ) 0.38 ( ) Asymmetry of disease 1.8 ( ) 0.61 ( ) Tremor 1.5 ( ) 0.47 ( )

41 Nomogram for Interpreting LR Plot patient s prior probability on left Draw straight line through LR for given test result Line points to posttest probability

42 70-year-old man Return to Case 1 History 3-month history of progressive tremor Difficulty writing letters Physical examination Bilateral tremor Otherwise well Continues to play golf

43 LR: Tremor History of tremor, LR = % Prior probability of Parkinson disease in 70-year-old man 1.3%-10% Posttest probability

44 Return to Case Scenario 1 Additional physical examination Glabella tap positive (LR = 4.5) Micrographia (LR = 2.8) Difficulty walking heel to toe (LR = 2.9)

45 LR: Glabella Tap/Heel to Toe Heel to toe, LR = 2.9 1% Prior probability of Parkinson disease in 70-year-old man Posttest probability 3% for Heel to toe

46 Return to Case 2 68-year-old man History 3-month history of right arm tremor Trouble getting up from chair Physical examination Rigidity Small steps, limited arm swing Limited facial expression

47 LR: Tremor Bradykinesia LR = 1.9 1% Pretest probability of Parkinson disease in 68-year-old man Posttest probability, 2%

48 Case Scenarios Both cases have many features of Parkinson disease. Given a 1% prior probability, single findings each individually increase likelihood of disease. However, clinical decisions are made based on multiple findings and follow-up over time. Positive symptoms and signs over time may justify a trial of empiric treatment.

49 Take home Classic features when present do help establish the diagnosis otremor origidity obradykinesia combined oloss of balance (postural instability) oresponse to L dopa

50 Take home Diagnosis of Parkinson disease remains challenging and relies on clinical evaluation, signs, and symptoms. Single findings may not alter the prior probability enough to direct diagnosis and management on their own. Combinations of findings, follow-up, and response to therapy guides clinical management, but such strategies have not been tested.