| Domain | Feature | Definition |
| Ocular motor dysfunction |
| O1 | Vertical supranuclear gaze palsy | A clear limitation of the range of voluntary gaze in the vertical more than in the horizontal plane, affecting both upgaze and downgaze, more than expected for age, which is overcome by activation with the vestibulo-ocular reflex; at later stages, the vestibulo-ocular reflex may be lost, or the maneuver prevented by nuchal rigidity. |
| O2 | Slow velocity of vertical saccades | Decreased velocity (and amplitude) of vertical greater than horizontal saccadic eye movements; this may be established by quantitative measurements of saccades, such as infrared oculography, or by bedside testing; gaze should be assessed by command ("Look at the flicking finger") rather than by pursuit ("Follow my finger"), with the target >20 degrees from the position of primary gaze; to be diagnostic, saccadic movements are slow enough for the examiner to see their movement (eye rotation), rather than just initial and final eye positions in normal subjects; a delay in saccade initiation is not considered slowing; findings are supported by slowed or absent fast components of vertical optokinetic nystagmus (ie, only the slow following component may be retained). |
| O3 | Frequent macro square wave jerks or "eyelid opening apraxia" | Macro square wave jerks are rapid involuntary saccadic intrusions during fixation, displacing the eye horizontally from the primary position, and returning it to the target after 200 to 300 milliseconds; most square wave jerks are <1 degree in amplitude and rare in healthy controls, but up to 3 to 4 degrees and more frequent (>10/minute) in PSP.[1] "Eyelid opening apraxia" is an inability to voluntarily initiate eyelid opening after a period of lid closure in the absence of involuntary forced eyelid closure (ie, blepharospasm); the term is written in quotation marks because the inability to initiate eyelid opening is often attributed to activation of the pretarsal component of the orbicularis oculi (ie, pretarsal blepharospasm) rather than failure to activate the levator palpebrae. |
| Postural instability |
| P1 | Repeated unprovoked falls within 3 years | Spontaneous loss of balance while standing, or history of more than one unprovoked fall, within 3 years after onset of PSP-related features. |
| P2 | Tendency to fall on the pull-test within 3 years | Tendency to fall on the pull-test if not caught by examiner, within 3 years after onset of PSP-related features. The test examines the response to a quick, forceful pull on the shoulders with the examiner standing behind the patient and the patient standing erect with eyes open and feet comfortably apart and parallel, as described in the MDS-UPDRS item 3.12. |
| P3 | More than two steps backward on the pull-test within 3 years | More than two steps backward, but unaided recovery, on the pull-test, within 3 years after onset of PSP-related features. |
| Akinesia |
| A1 | Progressive gait freezing within 3 years | Sudden and transient motor blocks or start hesitation are predominant within 3 years after onset of PSP-related symptoms, progressive and not responsive to levodopa; in the early disease course, akinesia may be present, but limb rigidity, tremor, and dementia are absent or mild. |
| A2 | Parkinsonism, akinetic-rigid, predominantly axial and levodopa resistant | Bradykinesia and rigidity with axial predominance, and levodopa resistance (refer to Clinical Clue CC1 for operationalized definition). |
| A3 | Parkinsonism, with tremor and/or asymmetric and/or levodopa responsive | Bradykinesia with rigidity and/or tremor, and/or asymmetric predominance of limbs, and/or levodopa responsiveness (refer to Clinical Clue CC1 for operationalized definition). |
| Cognitive dysfunction |
| C1 | Speech/language disorder | Defined as at least one of the following features, which has to be persistent (rather than transient): - Nonfluent/agrammatic variant of primary - Loss of grammar and/or telegraphic speech or writing progressive aphasia (nfaPPA) or
- Progressive apraxia of speech (AOS) - Effortful, halting speech with inconsistent speech sound errors and distortions or slow syllabically segmented prosodic speech patterns with spared single-word comprehension, object knowledge, and word retrieval during sentence repetition.
|
| C2 | Frontal cognitive/behavioral presentation | Defined as at least three of the following features, which have to be persistent (rather than transient): - Apathy - Reduced level of interest, initiative, and spontaneous activity; clearly apparent to informant or patient.
- Bradyphrenia - Slowed thinking; clearly apparent to informant or patient.
- Dysexecutive syndrome - Eg, reverse digit span, Trails B or Stroop test, Luria sequence (at least 1.5 standard deviations below mean of age- and education-adjusted norms).
- Reduced phonemic verbal fluency - Eg, "D, F, A, or S" words per minute (at least 1.5 standard deviations below mean of age- and education-adjusted norms).
- Impulsivity, disinhibition, or perseveration - Eg, socially inappropriate behaviors, overstuffing the mouth when eating, motor recklessness, applause sign, palilalia, echolalia.
|
| C3 | CBS | Defined as at least one sign each from the following two groups (may be asymmetric or symmetric): - Cortical signs
- Orobuccal or limb apraxia.
- Cortical sensory deficit.
- Alien limb phenomena (more than simple levitation.)
- Movement disorder signs
- Limb rigidity.
- Limb akinesia.
- Limb myoclonus.
|
| Clinical clues |
| CC1 | Levodopa resistance | Levodopa resistance is defined as improvement of the MDS-UPDRS motor scale by ≤30%; to fulfill this criterion patients should be assessed having been given at least 1000 mg (if tolerated) at least 1 month OR once patients have received this treatment they could be formally assessed following a challenge dose of at least 200 mg. |
| CC2 | Hypokinetic, spastic dysarthria | Slow, low volume and pitch, harsh voice. |
| CC3 | Dysphagia | Otherwise unexplained difficulty in swallowing, severe enough to request dietary adaptations. |
| CC4 | Photophobia | Intolerance to visual perception of light attributed to adaptative dysfunction. |
| Imaging findings |
| IF1 | Predominant midbrain atrophy or hypometabolism | Atrophy or hypometabolism predominant in midbrain relative to pons, as demonstrated, eg, by MRI or [18F]DG-PET. |
| IF2 | Postsynaptic striatal dopaminergic degeneration | Postsynaptic striatal dopaminergic degeneration, as demonstrated, eg, by [123I]IBZM-SPECT or [18F]-DMFP-PET. |
