Progressive Supranuclear Palsy¶
VERSION: 1.1 CREATED: January 30, 2026 REVISED: January 30, 2026 STATUS: Approved
DIAGNOSIS: Progressive Supranuclear Palsy (PSP)
ICD-10: G23.1 (Progressive supranuclear ophthalmoplegia [Steele-Richardson-Olszewski]), F02.80 (Dementia in other diseases classified elsewhere, without behavioral disturbance), F02.81 (Dementia in other diseases classified elsewhere, with behavioral disturbance), G25.9 (Extrapyramidal and movement disorder, unspecified)
CPT CODES: 85025 (CBC with differential), 80053 (CMP), 84443 (TSH), 82607 (Vitamin B12), 86592 (RPR/VDRL), 81003 (Urinalysis), 85652 (ESR), 82390 (Serum ceruloplasmin), 82525 (Serum copper), 87389 (HIV), 86618 (Lyme serology), 86235 (ANA), 82306 (Vitamin D), 83655 (Heavy metals (manganese, lead)), 70551 (MRI brain without contrast), 70450 (CT head without contrast), 70552 (MRI brain with contrast), 78830 (DaTscan), 78608 (FDG-PET brain), 78811 (Amyloid PET), 95810 (Polysomnography), 74230 (Videofluoroscopic swallow study (VFSS)), 92612 (FEES (fiberoptic endoscopic evaluation of swallowing)), 96132 (Neuropsychological testing), 95816 (EEG)
SYNONYMS: Progressive supranuclear palsy, PSP, Steele-Richardson-Olszewski syndrome, PSP-Richardson syndrome, PSP-RS, Richardson syndrome, supranuclear gaze palsy, supranuclear palsy, atypical parkinsonism, tauopathy, PSP-parkinsonism, PSP-P, PSP-progressive gait freezing, PSP-PGF, PSP-frontal, PSP-F, PSP-corticobasal syndrome, PSP-CBS, PSP-speech/language, PSP-SL, PSP-oculomotor, PSP-OM, PSP-postural instability, PSP-PI, nuclear palsy, vertical gaze palsy, downgaze palsy, 4-repeat tauopathy, subcortical parkinsonism
SCOPE: Diagnosis and comprehensive management of progressive supranuclear palsy in adults across ED, hospital, outpatient, and ICU settings. Covers MDS-PSP diagnostic criteria application, imaging workup, symptomatic pharmacotherapy (levodopa trial, symptomatic medications), fall prevention, dysphagia management, supportive care, and palliative care integration. Excludes other atypical parkinsonian syndromes (MSA, CBD, DLB) as primary diagnosis, drug-induced parkinsonism, and pediatric tauopathies.
KEY CLINICAL FEATURES:
- Vertical supranuclear gaze palsy (especially downgaze limitation; upgaze often affected first but less specific)
- Early postural instability with unexplained backward falls within first year
- Axial rigidity > limb rigidity (neck/trunk stiffness predominates)
- Symmetric parkinsonism with poor or absent levodopa response
- Pseudobulbar affect (involuntary laughing or crying)
- Frontal cognitive/behavioral changes (apathy, disinhibition, executive dysfunction)
- Dysarthria and dysphagia (early and progressive)
- Eyelid abnormalities (blepharospasm, apraxia of eyelid opening/closing)
- Axial extension posture (retrocollis, as opposed to flexed posture of PD)
- "Rocket sign": patient rises abruptly without planning and falls backward
- "Applause sign": inability to stop clapping after 3 claps (frontal lobe dysfunction)
MEDIAN SURVIVAL: 6-9 years from symptom onset (Richardson syndrome); longer for PSP-P and PSP-PGF variants
PSP CLINICAL VARIANTS (MDS-PSP Criteria):
| Variant | Abbreviation | Key Features |
|---|---|---|
| Richardson syndrome (classic) | PSP-RS | Early falls, vertical gaze palsy, axial rigidity, cognitive changes; most common |
| PSP-parkinsonism | PSP-P | Asymmetric onset, tremor may be present, initial levodopa response (transient); resembles PD |
| PSP-progressive gait freezing | PSP-PGF | Early gait freezing, postural instability; gaze palsy develops later |
| PSP-frontal | PSP-F | Prominent behavioral/cognitive changes (apathy, disinhibition); resembles bvFTD |
| PSP-corticobasal syndrome | PSP-CBS | Asymmetric limb apraxia, cortical sensory loss, alien limb; resembles CBD |
| PSP-speech/language | PSP-SL | Progressive nonfluent aphasia or apraxia of speech as presenting feature |
MDS-PSP DIAGNOSTIC CRITERIA (Hoglinger et al., 2017):
Basic Features (Required): - Gradually progressive disorder - Age at onset ≥40 years
Core Clinical Features (Organized by Domain):
| Domain | Feature |
|---|---|
| Ocular motor dysfunction (O) | O1: Vertical supranuclear gaze palsy; O2: Slow velocity of vertical saccades |
| Postural instability (P) | P1: Repeated unprovoked falls within 3 years; P2: Tendency to fall on pull test within 3 years |
| Akinesia (A) | A1: Progressive gait freezing within 3 years; A2: Parkinsonism, akinetic-rigid, predominantly axial, levodopa-resistant |
| Cognitive dysfunction (C) | C1: Speech/language (nonfluent/agrammatic or progressive apraxia of speech); C2: Frontal cognitive/behavioral (≥3 of: apathy, bradyphrenia, executive dysfunction, reduced verbal fluency, impulsivity, perseveration) |
Diagnostic Certainty Levels:
| Level | Requirements |
|---|---|
| Definite PSP | Neuropathologic confirmation (4-repeat tau) |
| Probable PSP-RS | O1 or O2, AND P1 or P2 |
| Probable PSP-P | O1 or O2, AND A2 (with initial levodopa response) |
| Possible PSP-RS | O1 or O2, OR P1 or P2 with A2 |
| Suggestive of PSP | O2 (slow vertical saccades) alone, OR A1 or A2 |
Exclusion Criteria: - Predominant and unexplained cerebellar ataxia - Predominant and unexplained autonomic failure - Structural lesion explaining features - Whipple disease - Drug-induced parkinsonism
PRIORITY KEY: STAT = Immediate | URGENT = Within hours | ROUTINE = Standard | EXT = Extended/atypical cases | - = Not applicable to this setting
═══════════════════════════════════════════════════════════════ SECTION A: ACTION ITEMS ═══════════════════════════════════════════════════════════════
1. LABORATORY WORKUP¶
1A. Essential/Core Labs¶
| Test | Rationale | Target Finding | ED | HOSP | OPD | ICU |
|---|---|---|---|---|---|---|
| CBC with differential (CPT 85025) | Baseline health; infection screen in falls workup | Normal | STAT | ROUTINE | ROUTINE | STAT |
| CMP (CPT 80053) | Electrolytes, hepatic/renal function for medication dosing | Normal | STAT | ROUTINE | ROUTINE | STAT |
| TSH (CPT 84443) | Hypothyroidism can cause slowness and gait dysfunction | Normal (0.4-4.0 mIU/L) | URGENT | ROUTINE | ROUTINE | - |
| Vitamin B12 (CPT 82607) | Deficiency causes myelopathy and gait instability | >400 pg/mL | URGENT | ROUTINE | ROUTINE | - |
| RPR/VDRL (CPT 86592) | Neurosyphilis in differential of vertical gaze palsy | Negative | - | ROUTINE | ROUTINE | - |
| Urinalysis (CPT 81003) | UTI as cause of acute worsening, delirium | Negative | STAT | ROUTINE | ROUTINE | STAT |
| ESR (CPT 85652) / CRP (CPT 86140) | Inflammatory/autoimmune cause of parkinsonism | Normal | - | ROUTINE | ROUTINE | - |
1B. Extended Workup (Second-line)¶
| Test | Rationale | Target Finding | ED | HOSP | OPD | ICU |
|---|---|---|---|---|---|---|
| Serum ceruloplasmin (CPT 82390) | Wilson disease if age <50 | 20-40 mg/dL | - | ROUTINE | ROUTINE | - |
| Serum copper (CPT 82525) | Wilson disease if ceruloplasmin abnormal | Normal | - | ROUTINE | ROUTINE | - |
| 24-hour urine copper | Wilson disease confirmation | <100 mcg/24h | - | EXT | EXT | - |
| HIV (CPT 87389) | HIV-associated parkinsonism | Negative | - | ROUTINE | ROUTINE | - |
| Lyme serology (CPT 86618) | Lyme disease in endemic areas (cranial neuropathy) | Negative | - | ROUTINE | ROUTINE | - |
| ANA (CPT 86235) | CNS lupus, autoimmune causes | Negative | - | ROUTINE | ROUTINE | - |
| Anti-neuronal antibodies (paraneoplastic panel) | Paraneoplastic syndrome causing parkinsonism or gaze palsy | Negative | - | EXT | EXT | - |
| Whipple disease PCR (Tropheryma whipplei) | Whipple disease mimics PSP (oculomasticatory myorhythmia, gaze palsy) | Negative | - | EXT | EXT | - |
| Vitamin D (CPT 82306) | Deficiency increases fall risk | >30 ng/mL | - | ROUTINE | ROUTINE | - |
1C. Specialized Testing¶
| Test | Rationale | Target Finding | ED | HOSP | OPD | ICU |
|---|---|---|---|---|---|---|
| Serum neurofilament light chain (NfL) | Emerging biomarker; elevated in neurodegeneration; may correlate with disease severity | Elevated (research only) | - | - | EXT | - |
| Genetic testing (MAPT gene) | Familial PSP rare; MAPT H1/H1 haplotype is risk factor | Informational | - | - | EXT | - |
| CSF total tau / phospho-tau | Research biomarker; may help differentiate tauopathies | Elevated in PSP | - | EXT | EXT | - |
| CSF Abeta-42 | Distinguish from Alzheimer-related pathology | Normal or mildly decreased | - | EXT | EXT | - |
| Heavy metals (manganese, lead) (CPT 83655) | Manganese-induced parkinsonism in occupational exposure | Negative | - | - | EXT | - |
2. DIAGNOSTIC IMAGING & STUDIES¶
2A. Essential/First-line¶
| Study | Timing | Target Finding | Contraindications | ED | HOSP | OPD | ICU |
|---|---|---|---|---|---|---|---|
| MRI brain without contrast (CPT 70551) | At diagnosis | Midbrain atrophy ("hummingbird sign" on sagittal, "morning glory sign" on axial); midbrain-to-pons ratio decreased; third ventricle dilation | Pacemaker, metal implants | STAT | ROUTINE | ROUTINE | - |
| CT head without contrast (CPT 70450) | If MRI unavailable; acute fall with head injury | Rule out hemorrhage, mass, hydrocephalus | None | STAT | STAT | - | STAT |
2B. Extended¶
| Study | Timing | Target Finding | Contraindications | ED | HOSP | OPD | ICU |
|---|---|---|---|---|---|---|---|
| MRI brain with contrast (CPT 70552) | If mass or infection suspected | Rule out structural lesion | Contrast allergy, renal disease | - | ROUTINE | ROUTINE | - |
| MRI brain volumetry / midbrain measurement | Supportive; diagnostic uncertainty | Midbrain area <70 mm2 on midsagittal; midbrain-to-pons ratio <0.52 (MRPI) | Per MRI | - | - | ROUTINE | - |
| DaTscan (CPT 78830) | Diagnostic uncertainty; PSP vs non-degenerative | Reduced striatal uptake (abnormal in PSP, PD, MSA) | Pregnancy, iodine allergy | - | - | ROUTINE | - |
| FDG-PET brain (CPT 78608) | Distinguish PSP from other parkinsonism | Frontal and midbrain hypometabolism; "frontal lobe syndrome" pattern | Per PET | - | - | EXT | - |
| Tau PET (flortaucipir/Tauvid) | Research; not yet validated for PSP specifically | 4R-tau deposition in basal ganglia, brainstem, cortex | Per PET | - | - | EXT | - |
| Amyloid PET (CPT 78811) | Rule out concurrent AD pathology | Negative in pure PSP | Per PET | - | - | EXT | - |
| MIBG cardiac scintigraphy | Distinguish PSP from PD (preserved in PSP, reduced in PD) | Normal cardiac uptake in PSP | Drugs affecting uptake | - | - | EXT | - |
2C. Specialized Studies¶
| Study | Timing | Target Finding | Contraindications | ED | HOSP | OPD | ICU |
|---|---|---|---|---|---|---|---|
| Polysomnography (CPT 95810) | If REM sleep behavior disorder suspected | RBD less common in PSP than PD/DLB | None | - | - | ROUTINE | - |
| Video-oculography / infrared oculography | Quantify saccade velocity; confirm vertical saccade slowing | Reduced vertical saccade velocity | None | - | - | ROUTINE | - |
| Videofluoroscopic swallow study (VFSS) (CPT 74230) | If dysphagia present; baseline and serial | Assess aspiration risk, pharyngeal residue | None | - | ROUTINE | ROUTINE | - |
| FEES (fiberoptic endoscopic evaluation of swallowing) (CPT 92612) | Alternative to VFSS; bedside evaluation | Silent aspiration, pooling | None | - | ROUTINE | ROUTINE | - |
| Neuropsychological testing (CPT 96132) | Baseline; characterize cognitive profile | Frontal-executive dysfunction; preserved memory early | None | - | - | ROUTINE | - |
| EEG (CPT 95816) | If seizures or myoclonus suspected | Usually normal or diffuse slowing | None | - | ROUTINE | ROUTINE | - |
3. TREATMENT¶
NO DISEASE-MODIFYING THERAPY EXISTS FOR PSP
All current treatments are symptomatic. Levodopa trial is recommended but benefit is limited (usually <30% of patients show modest response). Several clinical trials are ongoing targeting tau pathology.
3A. Acute/Emergent Treatment¶
| Treatment | Route | Indication | Dosing | Contraindications | Monitoring | ED | HOSP | OPD | ICU |
|---|---|---|---|---|---|---|---|---|---|
| Carbidopa/Levodopa (Sinemet) | PO | Levodopa responsiveness trial; required by MDS criteria for akinetic-rigid parkinsonism | 25/100 mg :: PO :: TID :: Start 25/100 mg TID with meals; titrate by 25/100 mg q1-2 weeks to 25/250 mg TID; adequate trial requires 800-1000 mg levodopa/day for ≥1 month; document response | Narrow-angle glaucoma; concurrent non-selective MAOIs | Nausea, orthostatic hypotension, dyskinesia (rare in PSP); document percent improvement | - | ROUTINE | ROUTINE | - |
| Carbidopa/Levodopa CR (Sinemet CR) | PO | Sustained-release option if GI intolerance to IR or for nocturnal dosing | 50/200 mg :: PO :: BID-TID :: 50/200 mg BID-TID; ~30% less bioavailable than IR; may combine with IR | Narrow-angle glaucoma; concurrent non-selective MAOIs | Nausea, orthostatic hypotension; less predictable absorption | - | ROUTINE | ROUTINE | - |
| Thickened liquids | PO | Dysphagia with thin liquid aspiration on swallow study | Per SLP recommendation :: PO :: per meal :: Nectar-thick, honey-thick, or pudding-thick per swallow study results; reassess as disease progresses | Patient refusal (goals of care discussion) | Weight, hydration status, aspiration events; serial swallow evaluations | ROUTINE | ROUTINE | ROUTINE | ROUTINE |
3B. Symptomatic/Maintenance Treatment¶
| Treatment | Route | Indication | Dosing | Contraindications | Monitoring | ED | HOSP | OPD | ICU |
|---|---|---|---|---|---|---|---|---|---|
| Amantadine | PO | Gait freezing, akinesia; may help some patients with motor symptoms | 100 mg :: PO :: BID :: Start 100 mg daily; increase to 100 mg BID-TID; avoid evening dosing (insomnia); max 300 mg/day; reduce dose in renal impairment (CrCl <50) | Severe renal impairment (CrCl <15); seizure history (relative); uncontrolled glaucoma | Livedo reticularis, peripheral edema, hallucinations, insomnia, confusion; renal function | - | ROUTINE | ROUTINE | - |
| OnabotulinumtoxinA (Botox) - blepharospasm | IM | Blepharospasm causing functional blindness; involuntary eyelid closure | 2.5-5 units/site :: IM :: q12 weeks :: 2.5-5 units per injection site in orbicularis oculi; total 10-30 units per eye; repeat q12 weeks; specialist administration | Infection at injection site; myasthenia gravis; aminoglycoside use | Ptosis, dry eye, excessive tearing, hematoma; reassess at each visit | - | - | ROUTINE | - |
| OnabotulinumtoxinA (Botox) - dystonia | IM | Dystonia (retrocollis, limb dystonia) causing pain or functional impairment | Dose varies by muscle :: IM :: q12 weeks :: EMG-guided injection; retrocollis: splenius capitis 50-200 units; dose per target muscle; repeat q12 weeks | Infection at injection site; myasthenia gravis; aminoglycoside use | Dysphagia (especially cervical injections), weakness, pain at injection site | - | - | ROUTINE | - |
| OnabotulinumtoxinA (Botox) - sialorrhea | IM | Sialorrhea (drooling) not responsive to oral anticholinergics | 30 units/parotid :: IM :: q12 weeks :: 30 units per parotid gland; 20 units per submandibular gland; repeat q12 weeks | Infection at injection site; myasthenia gravis | Dry mouth, dysphagia, jaw weakness | - | - | ROUTINE | - |
| Baclofen | PO | Axial rigidity, limb spasticity causing pain or functional impairment | 5 mg :: PO :: TID :: Start 5 mg TID; titrate by 5 mg/dose q3-5 days; max 80 mg/day; do NOT discontinue abruptly (risk of withdrawal seizures) | Renal impairment (reduce dose); seizure history (relative) | Sedation, weakness, confusion (especially elderly); renal function | - | ROUTINE | ROUTINE | - |
| Tizanidine | PO | Axial rigidity, spasticity as alternative to baclofen | 2 mg :: PO :: TID :: Start 2 mg at bedtime; titrate to 2-4 mg TID; max 36 mg/day; reduce dose in hepatic impairment | Hepatic impairment; concurrent CYP1A2 inhibitors (fluvoxamine, ciprofloxacin) | LFTs at baseline, 1, 3, 6 months; sedation, dry mouth, hypotension | - | ROUTINE | ROUTINE | - |
| Sertraline | PO | Depression common in PSP; first-line SSRI | 25 mg :: PO :: daily :: Start 25 mg daily; increase by 25 mg q1-2 weeks; target 50-100 mg daily; max 200 mg/day | Concurrent MAOIs; QT prolongation (relative) | GI bleeding risk, hyponatremia, serotonin syndrome; Na+ if elderly | - | ROUTINE | ROUTINE | - |
| Escitalopram | PO | Depression as alternative SSRI; well-tolerated | 5 mg :: PO :: daily :: Start 5 mg daily; increase to 10-20 mg daily; max 20 mg (QTc risk at higher doses) | Concurrent MAOIs; QT prolongation | QTc if risk factors; hyponatremia; GI bleeding | - | ROUTINE | ROUTINE | - |
| Dextromethorphan/Quinidine (Nuedexta) | PO | Pseudobulbar affect (involuntary laughing/crying); FDA-approved for PBA | 20/10 mg :: PO :: daily then BID :: Start 20/10 mg daily x 7 days, then increase to 20/10 mg BID; take at least q12 hours | QT prolongation; concurrent MAOIs; CYP2D6 poor metabolizers on quinidine | QTc at baseline and after dose increase; drug interactions (CYP2D6 substrates) | - | ROUTINE | ROUTINE | - |
| Modafinil | PO | Excessive daytime sleepiness, fatigue, and apathy in PSP | 100 mg :: PO :: daily :: Start 100 mg every morning; may increase to 200 mg daily; avoid afternoon dosing | Cardiac arrhythmia; hepatic impairment (reduce dose) | Blood pressure, heart rate; insomnia; headache | - | - | ROUTINE | - |
| Methylphenidate | PO | Apathy and abulia not responsive to other measures; off-label for frontal symptoms | 5 mg :: PO :: BID :: Start 5 mg in AM and at noon; titrate to 10 mg BID; max 20 mg BID; avoid afternoon dosing | Severe anxiety, agitation; cardiac arrhythmia; concurrent MAOIs | Heart rate, blood pressure, appetite, sleep; abuse potential (low in this population) | - | - | ROUTINE | - |
| Zolpidem | PO | Oculomotor dysfunction; limited evidence for transient improvement in saccades and motor function | 5 mg :: PO :: daily :: 5-10 mg once daily (trial dose); evidence is limited to case series; some patients show paradoxical improvement in motor and oculomotor function | Severe hepatic impairment; respiratory depression; myasthenia gravis | Sedation, falls (paradoxically may improve in some), confusion; short trial recommended | - | - | EXT | - |
| Donepezil | PO | Cognitive impairment in PSP; cholinergic deficit in PSP | 5 mg :: PO :: QHS :: Start 5 mg QHS x 4-6 weeks; may increase to 10 mg QHS; limited evidence in PSP but reasonable trial | Bradycardia; sick sinus syndrome; GI bleeding; peptic ulcer | Bradycardia, GI side effects (nausea, diarrhea), nightmares; heart rate | - | ROUTINE | ROUTINE | - |
| Rivastigmine patch (Exelon) | Transdermal | Cognitive impairment alternative to donepezil; may help attention and executive function | 4.6 mg/24h :: Transdermal :: daily :: Start 4.6 mg/24h patch; increase monthly to 9.5-13.3 mg/24h; patch preferred over oral (less GI side effects) | Bradycardia; sick sinus syndrome; GI bleeding | Skin irritation, GI effects, bradycardia; weight; heart rate | - | ROUTINE | ROUTINE | - |
| Quetiapine | PO | Agitation, psychosis, or behavioral disturbance in PSP; safest antipsychotic in parkinsonian syndromes | 12.5 mg :: PO :: QHS :: Start 12.5 mg QHS; titrate slowly to 25-100 mg QHS; lowest effective dose | QT prolongation; metabolic syndrome | QTc, fasting glucose, lipids, weight; sedation; increased mortality risk (black box warning in dementia) | - | ROUTINE | ROUTINE | - |
| Melatonin | PO | Insomnia and sleep-wake cycle disturbance; safe first-line sleep aid | 3 mg :: PO :: QHS :: 3-5 mg at bedtime; extended-release may be better for sleep maintenance | None significant | Daytime drowsiness (minimal) | - | ROUTINE | ROUTINE | - |
| Trazodone | PO | Insomnia as second-line; may help behavioral symptoms | 25 mg :: PO :: QHS :: Start 25-50 mg QHS; max 100 mg QHS for sleep | Orthostatic hypotension (caution in PSP with falls) | Sedation, orthostasis, priapism (rare) | - | ROUTINE | ROUTINE | - |
| Glycopyrrolate | PO | Sialorrhea (drooling) causing skin breakdown or aspiration risk | 1 mg :: PO :: BID :: Start 1 mg BID; titrate to 1-2 mg TID; max 8 mg/day | Narrow-angle glaucoma; urinary retention; bowel obstruction | Dry mouth (desired), urinary retention, constipation, tachycardia, cognitive worsening | - | ROUTINE | ROUTINE | - |
| Atropine 1% ophthalmic drops (sublingual) | SL | Sialorrhea; alternative to systemic anticholinergics with less cognitive effect | 1-2 drops :: SL :: TID :: 1-2 drops of 1% ophthalmic solution sublingual TID PRN drooling; local effect | Narrow-angle glaucoma | Dry mouth, tachycardia; minimal systemic absorption | - | ROUTINE | ROUTINE | - |
| Scopolamine patch (Transderm Scop) | Transdermal | Sialorrhea; transdermal delivery avoids swallowing difficulty | 1.5 mg :: Transdermal :: q72h :: 1.5 mg patch q72 hours; apply behind ear; rotate sides | Narrow-angle glaucoma; urinary retention | Dry mouth, blurred vision, confusion (especially elderly); urinary retention | - | ROUTINE | ROUTINE | - |
3C. Prophylactic/Preventive Treatment¶
| Treatment | Route | Indication | Dosing | Contraindications | Monitoring | ED | HOSP | OPD | ICU |
|---|---|---|---|---|---|---|---|---|---|
| Calcium + Vitamin D | PO | Osteoporosis prevention given high fall risk | 600 mg calcium + 1000 IU D3 :: PO :: BID :: Calcium carbonate 600 mg BID with meals + Vitamin D3 1000-2000 IU daily; total 1200 mg calcium/day | Hypercalcemia; renal stones (relative) | Calcium level, Vitamin D level annually; renal function | - | ROUTINE | ROUTINE | - |
| Bisphosphonate (alendronate) | PO | Osteoporosis treatment if T-score ≤ -2.5 or fragility fracture | 70 mg :: PO :: weekly :: 70 mg PO weekly; take on empty stomach with full glass water; remain upright 30 min | Esophageal disorders; inability to sit upright 30 min; GFR <30-35 | DEXA q2 years; jaw osteonecrosis (rare); esophageal symptoms | - | - | ROUTINE | - |
| Midodrine | PO | Orthostatic hypotension contributing to falls | 2.5 mg :: PO :: TID :: Start 2.5 mg TID; titrate to 5-10 mg TID; last dose by 4 PM (avoid supine hypertension); max 30 mg/day | Supine hypertension; urinary retention; severe cardiac disease | Supine blood pressure; urinary retention | - | ROUTINE | ROUTINE | - |
| Fludrocortisone | PO | Orthostatic hypotension as adjunct to midodrine or if midodrine insufficient | 0.1 mg :: PO :: daily :: Start 0.1 mg daily; may increase to 0.2 mg daily; max 0.3 mg/day | Heart failure; hypertension; hypokalemia | Potassium, edema, supine blood pressure, weight | - | ROUTINE | ROUTINE | - |
| Droxidopa (Northera) | PO | Neurogenic orthostatic hypotension not responsive to midodrine/fludrocortisone | 100 mg :: PO :: TID :: Start 100 mg TID; titrate by 100 mg/dose q24-48h; max 600 mg TID; last dose 5+ hours before bedtime | Supine hypertension (severe) | Supine blood pressure; headache; falls | - | ROUTINE | ROUTINE | - |
| Percutaneous endoscopic gastrostomy (PEG) tube | Surgical | Severe dysphagia with recurrent aspiration or inability to maintain nutrition/hydration | N/A :: Surgical :: once :: Discuss early when dysphagia progresses; ideally placed before FVC <50%; does not prevent aspiration but ensures nutrition; goals of care discussion essential | Coagulopathy; peritonitis; patient refusal | Tube site infection, displacement; weight; nutritional parameters | - | ROUTINE | EXT | - |
3D. Disease-Modifying Therapies¶
NO APPROVED DISEASE-MODIFYING THERAPIES
No disease-modifying therapy is currently approved for PSP. The agents below have been studied in clinical trials and failed to demonstrate efficacy. They are listed for reference only. Several tau-targeting agents (antisense oligonucleotides, tau immunotherapy) are in active clinical trials.
| Treatment | Route | Indication | Dosing | Pre-Treatment Requirements | Contraindications | Monitoring | ED | HOSP | OPD | ICU |
|---|---|---|---|---|---|---|---|---|---|---|
| Coenzyme Q10 (ubiquinone) | PO | Mitochondrial support; investigational in PSP; negative phase III trial but still used by some patients | 600 mg :: PO :: daily :: 600-1200 mg daily in divided doses with fatty food for absorption; no proven efficacy in PSP (QE3 trial negative) | None | None significant | GI upset; may reduce warfarin effect; no proven benefit | - | - | EXT | - |
| Davunetide (NAP) | N/A | Investigational tau-targeting neuroprotective agent; failed phase II/III | N/A :: N/A :: N/A :: Phase II/III completed; failed to show benefit; not currently available; historical reference | N/A | N/A | N/A | - | - | - | - |
| Riluzole | PO | Investigational in PSP; failed to show benefit in clinical trial | N/A :: PO :: N/A :: 50 mg BID trialed; NNIPPS trial showed no benefit in PSP; NOT recommended | N/A | Hepatic impairment | LFTs; neutrophil count; no proven benefit in PSP | - | - | - | - |
4. OTHER RECOMMENDATIONS¶
4A. Referrals & Consults¶
| Recommendation | ED | HOSP | OPD | ICU |
|---|---|---|---|---|
| Movement disorder specialist for diagnosis confirmation, MDS-PSP criteria application, and ongoing management optimization | - | ROUTINE | ROUTINE | - |
| Physical therapy for gait training, balance exercises, fall prevention strategies, and use of weighted walker | ROUTINE | ROUTINE | ROUTINE | - |
| Occupational therapy for ADL adaptation, home safety evaluation, and assistive device fitting | - | ROUTINE | ROUTINE | - |
| Speech-language pathology for swallow evaluation (VFSS or FEES), dysarthria management, and communication strategies | - | ROUTINE | ROUTINE | ROUTINE |
| Neuro-ophthalmology for evaluation of vertical gaze palsy, blepharospasm, and prism fitting for downgaze difficulty | - | - | ROUTINE | - |
| Neuropsychology for baseline cognitive assessment and characterization of frontal-executive dysfunction | - | - | ROUTINE | - |
| Psychiatry for depression, pseudobulbar affect, behavioral changes, and caregiver support | - | ROUTINE | ROUTINE | - |
| Social work for community resources, disability planning, caregiver respite, and long-term care planning | - | ROUTINE | ROUTINE | - |
| Palliative care for goals of care discussion, symptom management, and advance care planning early in disease course | - | ROUTINE | ROUTINE | ROUTINE |
| Nutrition/Dietitian for caloric optimization, texture-modified diet guidance, and PEG tube nutrition planning | - | ROUTINE | ROUTINE | ROUTINE |
| Pulmonology for respiratory function monitoring if respiratory compromise suspected | - | ROUTINE | ROUTINE | ROUTINE |
| Orthopedic surgery or trauma consult for fracture management in fall-related injuries | STAT | STAT | - | STAT |
4B. Patient/Family Instructions¶
| Recommendation | ED | HOSP | OPD | ICU |
|---|---|---|---|---|
| PSP is a progressive neurodegenerative disease; no cure exists but symptoms can be managed to improve quality of life | - | ROUTINE | ROUTINE | - |
| Falls are the most dangerous complication; use a weighted walker at all times when mobile to prevent backward falls | ROUTINE | ROUTINE | ROUTINE | - |
| Do NOT attempt to walk without assistive device or supervision given high risk of serious falls and head injury | ROUTINE | ROUTINE | ROUTINE | - |
| Return to ED immediately if fall with head injury, loss of consciousness, or new neurological symptoms (worsening speech, inability to swallow, breathing difficulty) | ROUTINE | ROUTINE | ROUTINE | - |
| Swallowing will gradually worsen; follow speech therapy recommendations for diet texture modification to prevent aspiration pneumonia | - | ROUTINE | ROUTINE | - |
| Eat in upright position, take small bites, allow adequate time for meals, and avoid talking while eating to reduce choking risk | - | ROUTINE | ROUTINE | - |
| Levodopa trial may provide modest benefit; take medication with meals and report any improvement in movement to your neurologist | - | ROUTINE | ROUTINE | - |
| Do NOT stop any prescribed medications abruptly without physician guidance | - | ROUTINE | ROUTINE | - |
| Report pseudobulbar affect (involuntary crying or laughing) as this is treatable with medication | - | ROUTINE | ROUTINE | - |
| Establish healthcare proxy, power of attorney, and advance directives early while patient can participate in decision-making | - | ROUTINE | ROUTINE | - |
| Contact CurePSP (curepsp.org) and PSP Foundation for patient and caregiver support resources | - | - | ROUTINE | - |
| Driving should be discontinued due to impaired downgaze, slowed saccades, and cognitive changes affecting reaction time | - | ROUTINE | ROUTINE | - |
4C. Lifestyle & Prevention¶
| Recommendation | ED | HOSP | OPD | ICU |
|---|---|---|---|---|
| Home safety evaluation: remove throw rugs, install grab bars in bathroom, improve lighting, eliminate trip hazards | - | ROUTINE | ROUTINE | - |
| Use weighted or rolling walker (weighted preferred to counteract backward falls tendency in PSP) | ROUTINE | ROUTINE | ROUTINE | - |
| Wear hip protectors to reduce fracture risk from falls | - | ROUTINE | ROUTINE | - |
| Regular physical activity within safe limits: seated exercises, recumbent cycling, supervised balance training | - | ROUTINE | ROUTINE | - |
| Head-of-bed elevation to 30 degrees for orthostatic hypotension management and aspiration prevention | - | ROUTINE | ROUTINE | ROUTINE |
| Maintain adequate hydration and nutrition; high-calorie supplementation if weight loss occurs | - | ROUTINE | ROUTINE | ROUTINE |
| Cognitive stimulation activities (puzzles, reading, social engagement) to support remaining cognitive function | - | ROUTINE | ROUTINE | - |
| Avoid sedating medications (benzodiazepines, anticholinergics, antihistamines) that increase fall risk and cognitive impairment | ROUTINE | ROUTINE | ROUTINE | ROUTINE |
| Caregiver respite planning; caregiver burnout is common in PSP given rapid functional decline | - | - | ROUTINE | - |
| Avoid excessive heat exposure which may worsen symptoms | - | - | ROUTINE | - |
═══════════════════════════════════════════════════════════════ SECTION B: REFERENCE (Expand as Needed) ═══════════════════════════════════════════════════════════════
5. DIFFERENTIAL DIAGNOSIS¶
| Alternative Diagnosis | Key Distinguishing Features | Tests to Differentiate |
|---|---|---|
| Parkinson's disease (PD) | Asymmetric onset, rest tremor, excellent levodopa response, limb > axial rigidity, no early falls, no vertical gaze palsy | DaTscan (abnormal in both), MIBG (reduced in PD, normal in PSP), MRI (no midbrain atrophy in PD), levodopa trial |
| Multiple system atrophy (MSA) | Early severe autonomic failure (orthostatic hypotension, urinary retention), cerebellar signs (MSA-C), stridor, poor levodopa response | MRI ("hot cross bun" sign, cerebellar atrophy), MIBG (preserved in MSA), autonomic testing |
| Corticobasal degeneration (CBD) | Markedly asymmetric, limb apraxia, alien limb phenomenon, cortical sensory loss, myoclonus, dystonia | MRI (asymmetric cortical atrophy), FDG-PET (asymmetric cortical hypometabolism) |
| Dementia with Lewy bodies (DLB) | Visual hallucinations, fluctuating cognition, REM sleep behavior disorder, dementia before or within 1 year of parkinsonism | DaTscan (abnormal), MIBG (reduced), EEG (posterior slow-wave activity) |
| Frontotemporal dementia - behavioral variant (bvFTD) | Prominent personality/behavioral changes, disinhibition, apathy, compulsions; no early motor features | MRI (frontal/temporal atrophy), FDG-PET (frontal hypometabolism), neuropsychological testing |
| Vascular parkinsonism | Stepwise progression, lower-body predominant, vascular risk factors, gait disorder, no tremor | MRI (extensive white matter disease, lacunar infarcts), vascular risk factors |
| Normal pressure hydrocephalus (NPH) | Magnetic gait (feet glued to floor), urinary incontinence, dementia; triad | MRI (ventriculomegaly out of proportion to atrophy), large volume LP tap test with gait improvement |
| Whipple disease | Oculomasticatory myorhythmia (pathognomonic), diarrhea, weight loss, arthralgias, vertical gaze palsy | PCR for Tropheryma whipplei (blood, CSF, small bowel biopsy); PAS-positive macrophages |
| Niemann-Pick type C | Vertical supranuclear gaze palsy, ataxia, dystonia; younger onset; organomegaly | Filipin staining of fibroblasts, NPC1/NPC2 genetic testing, oxysterol levels |
| Prion disease (CJD) | Rapid progression (weeks-months), myoclonus, cortical visual changes, MRI cortical ribboning | MRI (DWI cortical ribboning), EEG (periodic complexes), CSF RT-QuIC, 14-3-3 protein |
| Drug-induced parkinsonism | Temporal relationship to dopamine-blocking agents; symmetric; may include vertical gaze limitation with certain agents | Medication review; DaTscan (usually normal); improvement after drug withdrawal |
6. MONITORING PARAMETERS¶
| Parameter | Frequency | Target/Threshold | Action if Abnormal | ED | HOSP | OPD | ICU |
|---|---|---|---|---|---|---|---|
| PSP Rating Scale (PSPRS) | q6 months | Stable or slow decline | Adjust symptomatic therapy; reassess goals | - | ROUTINE | ROUTINE | - |
| MoCA or frontal assessment battery (FAB) | q6-12 months | ≥26 MoCA (or stable trend) | Cholinesterase inhibitor trial; neuropsychology referral | - | ROUTINE | ROUTINE | - |
| Falls frequency and severity | Each visit | Decreasing or stable | PT, home safety, assistive devices, hip protectors | ROUTINE | ROUTINE | ROUTINE | - |
| Orthostatic vital signs | Each visit | <20 mmHg SBP drop on standing | Midodrine, fludrocortisone, droxidopa, compression stockings | ROUTINE | ROUTINE | ROUTINE | ROUTINE |
| Swallowing function | q6 months or if worsening | Safe oral intake | Speech therapy; diet modification; PEG tube discussion | - | ROUTINE | ROUTINE | - |
| Weight | Each visit | Stable | Nutrition consult; caloric supplementation; PEG discussion | - | ROUTINE | ROUTINE | ROUTINE |
| Depression screening (PHQ-9) | q6 months | <5 | SSRI initiation or adjustment | - | ROUTINE | ROUTINE | - |
| Pseudobulbar affect assessment | Each visit | Controlled | Nuedexta initiation or dose adjustment | - | ROUTINE | ROUTINE | - |
| Functional independence (ADLs/IADLs) | q6 months | Maintaining function | OT, increase home support | - | ROUTINE | ROUTINE | - |
| Caregiver burden assessment | q6-12 months | Manageable | Respite care, support services, social work referral | - | - | ROUTINE | - |
| Visual function / gaze assessment | Each visit | Functional gaze | Prism glasses; neuro-ophthalmology referral | - | ROUTINE | ROUTINE | - |
| Bone density (DEXA) | Baseline and q2 years | T-score > -2.5 | Bisphosphonate therapy | - | - | ROUTINE | - |
| Respiratory function (FVC) | q6-12 months or if dyspnea | FVC >50% predicted | Pulmonology; BiPAP discussion | - | ROUTINE | ROUTINE | ROUTINE |
7. DISPOSITION CRITERIA¶
| Disposition | Criteria |
|---|---|
| Outpatient management | Most PSP patients; ambulatory (with assistive device), adequate home support, stable swallowing, no acute illness |
| Admit to hospital | Fall with serious injury (fracture, subdural hematoma, head injury); aspiration pneumonia; inability to maintain oral intake; acute delirium or rapid decline; UTI or other infection causing significant functional worsening |
| Discharge from hospital | Acute condition treated; safe swallowing or PEG in place; ambulatory with assistance; caregiver education completed; outpatient follow-up arranged; home safety plan in place |
| ICU admission | Aspiration pneumonia with respiratory failure; severe sepsis from aspiration or UTI; post-fall with intracranial hemorrhage requiring monitoring; respiratory failure requiring ventilatory support |
| Skilled nursing facility | Unable to safely live at home despite maximum support; recurrent falls despite interventions; severe dysphagia requiring constant supervision; advanced cognitive impairment |
| Hospice | End-stage PSP; bedbound; unable to communicate; recurrent aspiration; patient/family goals focused on comfort; estimated prognosis <6 months |
| Transfer to tertiary center | Diagnostic uncertainty requiring specialized movement disorder evaluation; consideration for clinical trial enrollment; complex symptom management |
8. EVIDENCE & REFERENCES¶
| Recommendation | Evidence Level | Source |
|---|---|---|
| MDS-PSP diagnostic criteria | Class II, Level B | Hoglinger et al., Mov Disord 2017 |
| Levodopa trial recommended in PSP workup | Class II, Level B | Respondek et al., Mov Disord 2014 |
| Limited levodopa response in PSP (<30% of patients) | Class II, Level B | Kompoliti et al., Mov Disord 1998 |
| MRI midbrain atrophy (hummingbird sign) supports PSP diagnosis | Class II, Level B | Massey et al., Neurology 2012 |
| Magnetic resonance parkinsonism index (MRPI) distinguishes PSP from PD | Class II, Level B | Quattrone et al., Neurology 2008 |
| MIBG cardiac scintigraphy normal in PSP, reduced in PD | Class III, Level C | Nagayama et al., Neurology 2005 |
| Amantadine may improve gait freezing in parkinsonian syndromes | Class III, Level C | Kompoliti et al., Neurology 1998 |
| Botulinum toxin effective for blepharospasm and dystonia | Class I, Level A | Simpson et al., Neurology 2008 (AAN guideline) |
| Botulinum toxin effective for sialorrhea in neurodegenerative disease | Class I, Level A | Jost et al., J Neurol 2019 |
| Dextromethorphan/quinidine (Nuedexta) FDA-approved for pseudobulbar affect | Class I, Level A | Pioro et al., Ann Neurol 2010 (STAR trial) |
| Cholinesterase inhibitors for cognitive symptoms in PSP | Class III, Level C | Litvan et al., Neurology 2001 |
| Coenzyme Q10 failed to show efficacy in PSP | Class I, Level A | Apetauerova et al., Neurology 2016 (QE3 trial) |
| Riluzole failed to show benefit in PSP | Class I, Level A | Bensimon et al., Lancet Neurol 2009 (NNIPPS trial) |
| Davunetide failed phase II/III in PSP | Class I, Level A | Boxer et al., Lancet Neurol 2014 |
| Weighted walker superior to standard walker for PSP backward falls | Class III, Level C | Bluett et al., Mov Disord 2020 |
| Early palliative care improves quality of life in neurodegenerative disease | Class I, Level A | Temel et al., NEJM 2010 (extrapolated from ALS/oncology) |
| PSP-RS most common variant; median survival 6-9 years | Class II, Level B | Respondek et al., Ann Neurol 2014 |
| PSP neuropathology: 4-repeat tauopathy with globose neurofibrillary tangles | Class I, Level A | Dickson et al., J Neuropathol Exp Neurol 2007 |
| Tau PET imaging in PSP shows subcortical uptake | Class III, Level C | Whitwell et al., Brain 2018 |
| Serum neurofilament light chain elevated in PSP | Class II, Level B | Rojas et al., Ann Clin Transl Neurol 2016 |
| Zolpidem transient improvement in oculomotor and motor function (case series) | Class IV, Level U | Daniele et al., Mov Disord 1999 |
| PSP clinical variants and tau pathology correlations | Class II, Level B | Kovacs et al., Acta Neuropathol 2020 |
| Physical therapy and exercise benefit in atypical parkinsonism | Class II, Level B | Zampieri and Di Fabio, Phys Ther 2008 |
| PEG placement timing in neurodegenerative dysphagia | Class III, Level C | ProGas Study Group, Lancet Neurol 2015 |
NOTES¶
- PSP is the most common atypical parkinsonian syndrome; prevalence approximately 5-7 per 100,000
- Diagnosis is clinical; no single test confirms PSP during life. Definitive diagnosis requires neuropathology (4-repeat tau, globose tangles)
- The "hummingbird sign" on midsagittal MRI (midbrain atrophy) and "morning glory sign" on axial MRI are supportive but not pathognomonic
- Levodopa trial is essential: titrate to 800-1000 mg/day for at least 1 month before declaring failure; document percent improvement
- PSP-P variant may initially respond to levodopa (up to 30% improvement) and can be misdiagnosed as PD for years
- Falls are the leading cause of morbidity and mortality; early investment in PT and assistive devices is critical
- Weighted walkers are preferred over standard walkers because they resist the backward tendency
- Dysphagia progresses inexorably; aspiration pneumonia is a leading cause of death. Early speech therapy and PEG discussion are essential
- No disease-modifying therapy exists; several tau-targeting agents are in clinical trials (antisense oligonucleotides, tau immunotherapy)
- Pseudobulbar affect is common and undertreated; Nuedexta is FDA-approved for this indication
- Goals of care and palliative care should be introduced early given median survival of 6-9 years
- Avoid dopamine-blocking agents (metoclopramide, haloperidol, typical antipsychotics) which worsen parkinsonism
CHANGE LOG¶
v1.1 (January 30, 2026) - Removed incorrect ICD-10 code G23.0 (Hallervorden-Spatz disease) per C1 - Fixed all structured dosing fields to proper format: [dose] :: [route] :: [frequency] :: [full_instructions] per C2/M1 - Restructured Section 3 from non-standard 3A-3F to standard 3A (Acute/Emergent), 3B (Symptomatic/Maintenance), 3C (Prophylactic/Preventive), 3D (Disease-Modifying Therapies) per C3/M2/R4 - Added Pre-Treatment Requirements column to Section 3D per standard DMT format per M3 - Reordered lab table columns to style guide format: Test | Rationale | Target Finding | ED | HOSP | OPD | ICU per S2/R2 - Reordered imaging table columns to style guide format: Study | Timing | Target Finding | Contraindications | ED | HOSP | OPD | ICU per S3/R3 - Added ICU to frontmatter setting field per S1/R6 - Added ICU column to Section 4A, 4B, 4C tables per S4/R7/R9 - Added ICU criteria to Section 7 Disposition (ICU admission row) for completeness - Added ICU coverage to CT head, urinalysis, CBC, CMP where clinically appropriate - Reordered Section 6 Monitoring columns to include venue columns last per standard format - Added REVISED date to metadata block per R8 - Consolidated dysphagia/sialorrhea treatments into Section 3B (symptomatic) and 3C (preventive) - Moved fall prevention medications (midodrine, fludrocortisone, droxidopa, calcium/vitamin D, bisphosphonate) to Section 3C - Moved PEG tube to Section 3C (preventive/planned procedure) - Added ICU venue coverage to palliative care, nutrition, pulmonology, SLP referrals in Section 4A - Added ICU coverage to relevant 4C lifestyle items (HOB elevation, hydration, avoid sedating meds) - Differentiated Botox indications with distinct row labels (blepharospasm, dystonia, sialorrhea)
v1.0 (January 30, 2026) - Initial template creation - Complete MDS-PSP diagnostic criteria with variant classification - Comprehensive levodopa trial protocol with adequate dose/duration - Symptomatic treatments for motor, cognitive, behavioral, and bulbar symptoms - Fall prevention strategies including weighted walker recommendation - Dysphagia management with PEG timing guidance - Investigational agents section (CoQ10, davunetide, riluzole - all negative) - Differential diagnosis including Whipple disease and Niemann-Pick type C - 24 evidence references - Palliative care integration