Parkinson’s Disease and

atypical Parkinsonism
 Scope

◉ Parkinson’s Disease
◉ Atypical parkinsonism
◉ Multi-system atrophy
◉ Progressive supranuclear palsy
◉ Advances in Parkinsonism

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Parkinson’s Disease
Progressive neurodegenerative disorder with diverse clinical features

Driven by dopaminergic depletion in substantia nigra and nigrostriatal

pathway

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 Bradykinesia
Gastrointestinal Olfactory
dysfunction dysfunction

Dermatologic
findings
Parkinson’s Pain and
sensory

Disease
Resting
Rigidity
tremor

Autonomic
Neuropsychiatry
dysfunction

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Bradykinesia

Rocky Mountain Movement Disorders Center, 7 Motor 5

Symptoms of Parkinsons Disease
Resting tremor

Rocky Mountain Movement Disorders Center, 7 Motor 6

Symptoms of Parkinsons Disease
Rigidity

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Diagnosis of PD

Armstrong and Okun, 2020 8

MRI findings in Parkinson’s
Disease Radiopaedia

◉ Loss of swallowtail sign

Chougar et al., 2020 9

Neuromelanin

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 Treatment of PD

Levodopa Nonergot MAO-B COMT Others

preparations dopamine inhibitors inhibitors
agonists

Carbidopa- Pramipexole Selegiline Entacapone Anticholinergi

levodopa (IR, (IR and XR) cs
SR, XR,
enteral and
inhaled)

Rotigotine Rasagiline Opicapone

Amantadine
Ropinirole Tolcapone Istradefylline

Clozapine
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Parkinsonism is a complex and

diverse neurodegenerative disorder
with no disease-modifying treatments

“
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Atypical Parkinsonism

“
 Secondary Parkinsonism

Drug-induced Vascular Infectious Autoimmune Neoplastic NPH Functional

Atypical
Parkinsonism

Multiple system Progressive Corticobasal

atrophy supranuclear palsy degeneration

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Multiple system atrophy

◉ Adult onset, fatal neurodegenerative disorder

◉ Progressive autonomic dysfunction, Parkinsonian
features, with cerebellar and pyramidal clinical
presentations in combination.
◉ Affects 4.4 people/100,000

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Etiology

◉ Sporadic disease with genetic predisposition.

◉ Genes such as COQ2, SHC2 and SNCA have been
identified in specific populations.

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Pathogenesis

Fanciulli and Wenning, 2015

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Clinical Manifestations

◉ 2 main subtypes,
Parkinsonian and
Cerebellar
◉ Motor vs non-motor
manifestations.
◉ Features against
MSA

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Diagnosis of MSA

◉ Challenging diagnosis
◉ Neuropathology as post-mortem
◉ Investigations – diffusion weighted MRI

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“Hot cross bun sign”
◉ Result of selective degeneration of transverse pontocerebellar tracts and median
pontine raphe nuclei

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Principles of therapy

◉ Symptomatic management
○ Mainstay includes levodopa therapy,
neurorehabilitation, midodrine for orthostatic
hypotension, glycopyrrolate for secretions.
◉ No disease-modifying agents currently
○ Research currently focusing on targeting a-syn,
neuroinflammation and neural loss.

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Progressive Supranuclear Palsy

◉ Second most common cause of Parkinsonism

◉ Classical features of PSP include
○ Vertical gaze palsy
○ Pseudobulbar palsy
○ Axial rigidity
○ Cognitive impairment

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Vertical gaze palsy

PSPAssociation 23
Features of PSP

PSPAssociation 24
 Diagnosis

◉ Pre-symptomatic phase
◉ Suggestive of PSP
○ Patient may have not have PSP,
Richardson Syndrome or a variant PSP
syndrome.

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Pathogenesis

◉ PSP is a sporadic disease

○ Genetic studies have identified MAPT encoding the tau
protein as the greatest risk.
◉ GWAS studies have shown other genetic risk
factors

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Biomarkers

◉ Identification of biomarkers has largely been

possible through autopsy.
◉ Imaging
○ Atrophy of the midbrain and cerebellar peduncles on
MRI
○ PET-FDG to tau
◉ Slowing of vertical saccades compared to
horizontal
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MRI of PD Mimics

Radiopaedia
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Treatment

◉ Symptomatic management
◉ Disease modifying agents targeting tau protein or
mitochondrial dysfunction
○ Ongoing clinical trials but no effective treatment as of
yet.

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 Advances in
Parkinson’s Disease
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Teaching an old dog new tricks

◉ Exenatide (GLP-1 agonist)

○ Reduced microglial activation, neuroinflammation,
reducing oxidative stress and promotion of
neurogenesis.
◉ Azathioprine, dihydropyridine CCB and terazosin
have been considered with mixed results

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Immunotherapy

◉ Reduce levels of a-synuclein

○ Prasinezumab
■ Targeting C-terminus of a-synuclein
○ AFFITOPE PD01A
■ A vaccine designed to mount an immune response
against a-synuclein.

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Conclusion

◉ Parkinsonism is no longer defined by its classical

motor features
◉ Differentiating atypical Parkinsonism and
Parkinson’s Disease remains an ongoing
challenge.
◉ Current management remains primarily
symptomatic
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References

◉ Armstrong, M. and Okun, M., 2020. Diagnosis and Treatment of Parkinson Disease. JAMA,
323(6), p.548.
◉ Boxer, A., Yu, J., Golbe, L., Litvan, I., Lang, A. and Höglinger, G., 2017. Advances in progressive
supranuclear palsy: new diagnostic criteria, biomarkers, and therapeutic approaches. The
Lancet Neurology, 16(7), pp.552-563.
◉ Chougar, L., Pyatigorskaya, N., Degos, B., Grabli, D. and Lehéricy, S., 2020. The Role of Magnetic
Resonance Imaging for the Diagnosis of Atypical Parkinsonism. Frontiers in Neurology, 11.
◉ Fanciulli, A. and Wenning, G., 2015. Multiple-System Atrophy. New England Journal of Medicine,
372(3), pp.249-263.
◉ Lubarsky, M. and Juncos, J., 2008. Progressive Supranuclear Palsy. The Neurologist, 14(2), pp.79-
88.
◉ Stoker, T. and Barker, R., 2020. Recent developments in the treatment of Parkinson's
Disease. F1000Research, 9, p.862.
◉ Tolosa, E., Garrido, A., Scholz, S. and Poewe, W., 2021. Challenges in the diagnosis of Parkinson's
disease. The Lancet Neurology, 20(5), pp.385-397.

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Thank you!
Any questions ?

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