Progressive Supranuclear Palsy (PSP)

Primer

Progressive Supranuclear Palsy (PSP) is a neurodegenerative disorder characterized by early postural instability, leading to falls, and a characteristic vertical supranuclear-gaze palsy on physical exam. It is classified as an atypical parkinsonian syndrome (or Parkinson's Plus).

Symptoms

Pseudobulbar signs may be present, and retropulsion is often prominent. Cognitive testing will show psychomotor slowing, poor working memory, and executive dysfunction.

Diagnostic Criteria

NINDS-SPSP Criteria

The National Institute of Neurological Disorders and Stroke and Society for PSP (NINDS-SPSP) criteria are the most widely used criteria for the diagnosis of PSP.[1]

NINDS-SPSP PSP Criteria

Litvan, I., et al. Clinical research criteria for the diagnosis of progressive supranuclear palsy (Steele-Richardson-Olszewski syndrome) report of the NINDS-SPSP international workshop. Neurology 47.1 (1996): 1-9.
Symptoms
Probable PSP Vertical supranuclear gaze palsy plus postural instability and falls within the first year of symptom onset to diagnosis.
Possible PSP Supranuclear gaze palsy or a combination of slow vertical saccades and postural instability with falls within the first year.

MDS Criteria

The International Parkinson and Movement Disorder Society (MDS)-endorsed PSP Study Group set out to provide an evidence and consensus-based revision of the NINDS-SPSP criteria in 2017, with a much more comprehensive set of criteria.[2]

Basic Features: Core Inclusion and Exclusion Criteria

Höglinger, Günter U., et al. Clinical diagnosis of progressive supranuclear palsy: the movement disorder society criteria. Movement Disorders 32.6 (2017): 853-864.
Mandatory inclusion criteria 1. Sporadic occurrence
2. Age 40 or older at onset of first PSP-related symptom
3. Gradual progression of PSP-related symptoms
Mandatory exclusion criteria Clinical findings
1. Predominant, otherwise unexplained impairment of episodic memory, suggestive of Alzheimer's Disease (AD)
2. Predominant, otherwise unexplained autonomic failure, e.g., orthostatic hypotension (orthostatic reduction in blood pressure after 3 minutes standing 30 mm Hg systolic or 15 mm Hg diastolic), suggestive of multiple system atrophy or Lewy body disease
3. Predominant, otherwise unexplained visual hallucinations or fluctuations in alertness, suggestive of dementia with Lewy bodies
4. Predominant, otherwise unexplained multisegmental upper and lower motor neuron signs, suggestive of motor neuron disease (pure upper motor neuron signs are not an exclusion criterion)
5. Sudden onset or step-wise or rapid progression of symptoms, in conjunction with corresponding imaging or laboratory findings, suggestive of vascular etiology, autoimmune encephalitis, metabolic encephalopathies, or prion disease
6. History of encephalitis
7. Prominent appendicular ataxia
8. Identifiable cause of postural instability, e.g., primary sensory deficit, vestibular dysfunction,
severe spasticity, or lower motor neuron syndrome

Imaging findings
1. Severe leukoencephalopathy, evidenced by cerebral imaging
2. Relevant structural abnormality, e.g., normal pressure or obstructive hydrocephalus; basal ganglia, diencephalic, mesencephalic, pontine or medullary infarctions, hemorrhages, hypoxic-ischemic lesions, tumors, or malformations

Core Clinical Features

Höglinger, Günter U., et al. Clinical diagnosis of progressive supranuclear palsy: the movement disorder society criteria. Movement Disorders 32.6 (2017): 853-864.
Levels of Certainty Ocular Motor Dysfunction Postural Instability Akinesia Cognitive Dysfunction
Level 1 O1: Vertical supranuclear gaze palsy P1: Repeated unprovoked falls within 3 years A1: Progressive gait freezing
within 3 years 		C1: Speech/language disorder (i.e. - nonfluent/agrammatic variant of primary progressive aphasia or progressive apraxia of speech)
Level 2 O2: Slow velocity of vertical saccades P2: Tendency to fall on the pull-test within 3 year A2: Parkinsonism, akinetic-rigid,
predominantly axial, and
levodopa resistant 		C2: Frontal cognitive/behavioural presentation
Level 3 O3: Frequent macro square wave jerks or
“eyelid opening apraxia” 		P3: More than two steps backward on the pull-test within 3 years A3: Parkinsonism, with tremor and/or asymmetric and/or levodopa responsive C3: Corticobasal syndrome
Presumed levels of certainty (1 [highest], 2 [mid], and 3 [lowest]) that contribute to the diagnosis of PSP

Pathophysiology

PSP is due to the intracerebral aggregation of the microtubule-associated protein tau (MAPT), predominantly involving isoforms with four microtubule-binding repeats (4R-tau), in neurofibrillary tangles, oligoden- drocytic coils, and, specifically, astrocytic tufts. The definite diagnosis of PSP requires a post-mortem neuropathological examination.

References

1) Litvan, I., Agid, Y., Calne, D., Campbell, G., Dubois, B., Duvoisin, R. C., ... & Hallett, M. (1996). Clinical research criteria for the diagnosis of progressive supranuclear palsy (Steele-Richardson-Olszewski syndrome) report of the NINDS-SPSP international workshop. Neurology, 47(1), 1-9.
2) Hoglinger, Gunter U. et al. “Clinical Diagnosis of Progressive Supranuclear Palsy: The Movement Disorder Society Criteria.” Movement disorders : official journal of the Movement Disorder Society 32.6 (2017): 853–864. PMC. Web. 16 Sept. 2018.