Parkinson Mimics

1. Parkinson Mimics Denise S. Taylor, DO Athens Neurological Associates

2. Disclosures • Speakers bureau for UBC

3. Objectives • Recognize the clinical features, pathophysiology and treatment options of the spectrum of parkinsonian syndromes.

4. Hypokinetic Movement Disorders • Parkinson disease and its related syndromes are the prototypic hypokinetic movement disorders.

5. Parkinsonian syndromes Lewy bodies are pathologic intracytoplasmic inclusions made primarily of alpha synuclein, and are the pathologic hallmark of the synucleinopathies: • Idiopathic Parkinson disease • Multiple system atrophy • Dementia with Lewy bodies

6. Parkinsonian syndromes Filamentous taupositive intracytoplasmic inclusions, in contrast, are characteristic of the tauopathies: Progressive supranuclearpalsy Corticobasal degeneration

7. Cardinal Symptoms Non-motor features • Bradykinesia • Rigidity • Tremor • Postural instability • Autonomic dysfunction • Altered sense of smell • Sleep disturbances • Cognitive changes • Mood changes • Visual dysfunction Hypokinetic Movement Disorders

8. After the introduction of levodpa to treat PD in the late 1960’s the pathologies and clinical pictures of dopamine deficiency syndromes broadened. • Clinicians identified patients with signs of dopamine deficiency but unlike PD had minimal or no improvement with levodopa. • As a group they are called atypical parkinsonism.

9. Atypical Parkisnonism Progressive Supranuclear Palsy (PSP)Multiple System Atrophy (MSA) Corticobasal Degeneration (CBD) • PSP is the most common followed by MSA and CBD. • At this time PSP, CBD, and MSA are difficult to accurately clinically diagnose and many of the larger studies are based on autopsy.

10. Epidemiology and Genetics • Largest community based autopsy study of 233 cases: • PSP 15.8% of prevalence of PD • MSA 4.6% of prevalence of PD • CBD 2.1% of prevalence of PD • Recently small number of rare genetic conditions have been identified: • MAPT and PGRN (tau) • C9orf72, TARDBP, CHMP2B

11. Progressive Supranuclear Palsy • PSP is a Parkinson-plus syndrome mediated by the accumulation of tau protein. (PD is a synucleinopathy)

12. Progressive Supranuclear Palsy • Early impairments in vertical saccades, prominent frontal lobe dysfunction, and significant axial rigidity with postural instability and frequent falls. • Eventually causing a complete ophthalmoparesis. • Surprised facial expression secondary to facial dystonia and decreased eye blinks. • Axial rigidity results in oropharyngeal dysfunction with dysphagia and dysarthria.

14. Progressive Supranuclear Palsy • MRI may demonstrate generalized atrophy, most prominent in the midbrain; the “hummingbird sign” on mid-sagittal section, indicating pronounced midbrain atrophy, is characteristic of PSP.

15. Progressive Supranuclear Palsy • Course can vary from 2 years to 28 years, mean 8.7 years. • Life threatening symptoms: • Loss of balance leading to falls • Aspiration • Infection due to pressure ulcers. • Treatment is symptomatic, there are no disease modifying treatments at this time; this includes PSP, CBD, and MSA.

16. PSP March 2002: Dudley Moore, died age 66, from complications (pneumonia) of PSP. BBC News

17. Corticobasal Degeneration • Tauopathy • Mean age of onset 61-64 years. 62 yo man referred for F-18 (FDG-PET) with a diagnosis of parkinsonian syndrome. Markedly right-brain hemispheric hypometabolism also involving basal ganglia.

18. CorticobasalDegeneration • Similar to PD it is typically asymmetric with prominent early bradykinesia and asymmetric rigidity typically without tremor. • Focal or hemidystonia, may be painful, developing gradually but often leading to contractures. • Speech is hesitant and dysarthric • Apraxia is a prominent feature with ideomotor apraxia most common and characterized by an inability to perform goal-directed movements despite normal understanding.

19. Corticobasal Degeneration • Report extremity “jerks” describing cortical myoclonus which can be spontaneous or reflex • Alien limb phenomenon • Involuntary movements of a limb together with the patient’s feeling that the limb does not belong to them.

20. Corticobasal Degeneration • Asymmetric cortical atrophy usually in the frontoparietal region with relative sparing of the occipital lobes.

21. Multiple System Atrophy • Previously known as: • Olivopontocerebellar degeneration • Striatonigral degeneration • Shy-Dragersyndrome

22. Multiple System Atrophy • PSP and CBD have overlapping symptoms with PD despite having pathology including misfolded tau. • MSA also shares symptoms with PD and its pathology includes misfolded alpha-synuclein.

23. Multiple System Atrophy • MSA tends to present during middle age. • Most progress rapidly - more than 40% diagnosed with probable MSA were severely disabled or used a wheelchair by 5 yeas after onset. • Patients with cerebellar deficit predominance seem to progress more slowly.

24. Multiple System Atrophy Bradykinesia and rigidity are prominent but are typically symmetric compared to the asymmetry of PD. Postural instability often seen early, present within three years of symptom onset. Prominent autonomic dysfunction: orthostatic hypotension urinary incontinence/retention anhidrosis impotence REM Behavior Disorder.

25. Multiple System Atrophy Risk for anoxic brain damage from laryngeal stridor, often occurring at night, and cardiopulmonary arrest due to autonomic dysfunction.

26. Treatment: PSP, MSA and CBD • Since there is no cure tx is symptomatic. • Dopaminergic agents often worsen orthostasis. • Salt, fludrocortisone, midodrine, desmopressin may cause hypertension. • Botulinum toxin can treat apraxia of eyelid opening, dystonia, rigidity and sialorrhea. • Pseudobulbar can be treated with tricyclics or dextromethorphan/quinidine. • Depression: patients will not tolerate dopamine receptor blocking agents. • Constipation: high fiber diet, laxative, polyethylene glyol

27. Essential Tremor • Most common movement disorder in the US, with a prevalence of around 5%. • Kinetic Tremor, usually slightly asymmetric • Upper extremities followed by the head, neck, voice, and lower extremities. • Postural tremor is typicalbut it typically persists into activity. • Strong familial association, with around 50% of patients having a family history.

28. Essential Tremor • Limb tremor can be eliminated with resting the arms at the side. • Head/neck tremor can be abated with lying flat. • Both may persist at rest in later stages of the disease.

29. Essential Tremor • Diagnosis = typical phenomenology, family history, and improvement with alcohol or appropriate pharmacotherapy. • Laboratory testing, electrodiagnostic studies, and imaging are unnecessary to make a diagnosis, though thyroid function testing should be considered. • Prescription or illicit stimulant use should also be considered in the evaluation, as worsening of physiologic tremor seen with these substances may mimic ET.

30. Essential Tremor • Common drugs that exacerbate action tremor: • Lithium • Prednisone • Valproate • Tobacco • Caffeine • Cyclosporine • Levothyroxine

31. Essential Tremor

32. In the 1980s, Schulz complained that "sometimes my hand shakes so much I have to hold my wrist to draw." This led to an erroneous impression that Schulz had Parkinson's disease. According to a letter from his physician, placed in the Archives of the Charles M. Schulz Museum by his widow, Schulz had essential tremor, a condition alleviated by beta blockers. Schulz still insisted on writing and drawing the strip by himself, resulting in noticeably shakier lines over time. Charles M. Schulz – Wikipedia

33. Essential Tremor vs. PD • Absence of: • Rigidity • Hypomimia • Bradykinesia accompanied by decrement (finger tap) • Dystonic postures • Dysarthric speech • Nystagmus

35. Normal Pressure Hydrocephalus • Pathologically enlarged ventricular size with normal opening pressure on LP. • Form of communicating hydrocephalus; no structural blockage of CSF circulation.

36. Normal Pressure Hydrocephalus • Rare condition, estimated from 2 to 20 per million per year. • Idiopathic NPH increases in prevalence with age and most common >60 years.

37. Pathophysiology: NPH • Idiopathic NPH • Decompensated congenital hydrocephalus • Cerebrovascular disease • Decreased CSF absorption • Increased central venous pressure • Secondary NPH • Impaired absorption • SAH or IVH • Meningitis • Paget disease at skull base

38. Normal Pressure Hydrocephalus • Classic triad: • Dementia • Psychomotor slowing, impaired executive function, apathy, decreased attention/concentration • Gait disturbance (must be predominant problem) • Magnetic, small stepps, wide base, difficulty turning • Urinary Incontinence • Urgency rather than incontinence may be present at early stages • These symptoms believed to arise from dysfunction of supplementary motor areas of frontal lobe and periventricular white matter tracts.

40. High Volume LP: NPH • 30-50mL CSF removed with documentation of gait function before and 30-60min after the LP. • Gait speed, stride length, number of steps to turn. • Documented improvement in one or more of these measures suggests better outcome after placement of ventriculoperitoneal shunt. Positive predictive value 90-100%.

41. Tim Conway was diagnosed with NPH in 2009. He had shunt surgery which helped him considerably and allowed him to return to show business temporarily in 2011, but over time, he developed progressive dementia.  In 2015, he was treated with a new type of valve to drain the fluid from his brain and his dizziness, nausea and walking problems improved. The symptoms worsened in 2018 and he had additional brain surgery in September 2018, but he remained bedridden with a diagnosis of dementia and required 24-hours-a-day medical care. He died on May 14, 2019 at age 85, with the cause of death given as complications of NPH. WebMD

42. Refrences • Adams RD, van BogaertL, van der Eeken H. Nigro-striate and cerebello-nigro-strate degeneration. PsychiatNeruo (Basel) 1961; 142:219-259. • Armstrong MJ. Progressive supranuclear palsy and update. CurrNeurolNeurosci Rep 2018;18(3):12. • Armstrong MJ, Livtan I, Lang AE, et al. Criteria for the diagnosis of corticobasal degeneration. Neurology 2013;80(5):496-503. • Bhatia KP, Bain P, Bajaj N, et al. Consensus Statement on the classification of tremors from the task force on tremor of the International Parkinson and Moement Disorder Society. MovDisord 2018;33(1):75-87. • Espay AJ. Da Prat GA. Dwivedi AK, et al. Deconstructing normal pressure hydrocephalus: Ventriculomegaly as early sign of neurodegeneration. Ann Neurol 2017:82:503. • Hoginger GU, Respondek G. Stamelou M, et al. Clinical diagnosis of progressive supranuclear palsy: the Movement Disorder Society criteria. Mov Disorder 2017;32(6)853-864. • Jaraj D. Rabiei K. Marlow T. et al. Prevalence of idiopathic normal pressure hydrocephalus. Neurology 2014:82:1449. • Lantos PL. The definition of multiple system atrophy: A review of recent developments.J Neuropathology ExpNeurol 1998;57(12):1099-1111. • Respondek G, Stamelou M, Kruz C eet al. The phenotypic spectrum of progressive supranuclear palsy: a retrospective multicenter study of 100 definite cases. MovDisord 214: 29(14):758-766. • Steele JC, Richardson JC, Olszewski J. Progresivesupranuclear palsy. A heterogeneous degeneration involing the brain stem, basal ganglia, and cerebellum with vertical gaze and pseudobulbar palsy, nuchal dystonia and dementia. Arch Neurol 1964;10:333-359.

43. Videos: • links.lww.com/CONT/A278 • links.lww.com/CONT/A279 • links.lww.com/CONT/A56 • links.lww.com/CONT/A204 • links.lww.com/CONT/A283 American Academy of Neurology Continuum