Progressive supranuclear palsy — clinical features, management and prognosis

High-Yield Points (Textbook)

Source: Pathy's 6th ed., Chapters 53 (Table 53.2, Figure 53.1) and 46; Essentials of Clinical Geriatrics 7th ed., Table 6-7.

Definition and importance

Clinical features

Distinguishing PSP from Parkinson's disease

Feature Parkinson's disease Progressive supranuclear palsy Onset pattern Asymmetric or unilateral Symmetric from the outset Rest tremor Characteristic, 4–6 Hz Infrequent Rigidity Limb-predominant Axial (spinal) predominant, with neck dystonia Falls Late, in advanced disease Early and repeated Eye movements Normal (apart from age-related upgaze limitation) Vertical — especially downgaze — supranuclear palsy; impaired saccades; eyelid control problems Levodopa response Excellent (70–100%), sustained for years Unresponsive Cognition Dementia only after several years Personality change and dementia as the disease progresses MRI Usually unremarkable Midbrain atrophy — convex instead of concave outline Ioflupane SPECT Abnormal Abnormal (does not separate the two)

Management

Prognosis

Latest Updates (2023–Present)

PSP is now defined as a spectrum, not a single syndrome. The MDS-PSP criteria operationalise diagnosis across four functional domains — ocular motor dysfunction, postural instability, akinesia and cognitive dysfunction — with defined levels of certainty and eight clinical variants, including PSP-RS (Richardson's syndrome), PSP-P (parkinsonism), PSP-PGF (progressive gait freezing) and PSP-CBS (corticobasal syndrome). The early "suggestive of PSP" category was prospectively validated in the DESCRIBE-PSP and ProPSP cohorts (Quattrone et al., Movement Disorders 2025). Pathology is a 4-repeat tauopathy. PSP is characterised by accumulation of abnormal 4-repeat (4R) tau; the MAPT H1 haplotype is the major genetic risk factor.

Prognosis is now subtype-specific — a high-yield update. A global systematic review (Kukkle et al., Movement Disorders Clinical Practice 2026) reports global prevalence 5–6.4 per 100,000, with PSP-RS progressing rapidly with survival of 5–7 years, while PSP-P has a milder course with survival of 8–12 years. Regional differences reflect MAPT haplotype frequency, dietary neurotoxins, industrial pollutants and access to care. Biomarkers. Second-generation tau-PET with 18F-PI-2620 detects 4R tau (basal ganglia readout) and predicts subsequent increases in diagnostic certainty (LMU Munich prospective cohort). Fluid biomarkers — neurofilament light chain (NfL) and GFAP measured on the SIMOA platform — track progression and are being used as trial endpoints (Brain Communications 2025). Therapeutic pipeline. There is still no approved disease-modifying therapy. Tau-directed strategies — anti-tau antibodies, antisense oligonucleotides and sodium selenate (SEL003 trial) — are in trial. Reasons for past failures include late-stage intervention, poor patient selection, absence of prodromal biomarkers and inadequate outcome measures.

Indian relevance: Indian movement-disorder centres contributed to the 2026 global review; PSP is under-recognised in India, and diagnostic accuracy has improved measurably since adoption of the MDS-PSP criteria. Tau-PET is not available outside a few research centres, so MRI midbrain measures and clinical criteria remain the practical tools.

Current Practice Update

Aspect Textbook position (Pathy's 6th ed.) Current evidence-based practice Concept of the disease A single disorder: gaze palsy, early falls, axial rigidity A spectrum of 4R-tauopathy syndromes with eight recognised clinical variants Diagnostic criteria Clinical description only MDS-PSP criteria with four domains, certainty levels and a "suggestive of PSP" early category Pathological basis Not specified in the parkinsonism chapter Explicitly a 4-repeat tauopathy, MAPT H1 haplotype the major genetic risk Investigations MRI midbrain atrophy; ocular electrophysiology Add 18F-PI-2620 tau-PET and plasma/CSF NfL and GFAP — research and tertiary use Prognosis Progressive, unspecified duration Subtype-specific: PSP-RS 5–7 years, PSP-P 8–12 years Treatment Symptomatic, levodopa-unresponsive Unchanged — no disease-modifying therapy; tau-directed agents in trial Extra Points to Remember — this topic recurs Mnemonic for the classical (Richardson's) syndrome — "PSP FALLS": Postural instability with early falls; Supranuclear vertical gaze palsy (downgaze first); Pseudobulbar features and personality change; Falls in the first year; Axial rigidity and retrocollis; Levodopa non-response; Late dysphagia and dementia; Saccades impaired with no tremor.

The three-line answer if asked in viva: "PSP is a sporadic 4-repeat tauopathy presenting with early falls, vertical supranuclear gaze palsy, axial rigidity and levodopa non-response; MRI shows midbrain atrophy with a convex rather than concave outline; management is symptomatic, and Richardson's syndrome carries a survival of 5–7 years."

The single best discriminator to state first is not the gaze palsy (which may appear late) but early falls within the first year in a symmetric, tremor-free, levodopa-unresponsive parkinsonian patient.

Radiological signs worth naming: hummingbird/penguin sign on sagittal MRI, morning glory sign on axial MRI, and the Magnetic Resonance Parkinsonism Index (MRPI) as a quantitative midbrain–pons measure.

Do not confuse the supranuclear palsy of PSP (voluntary gaze lost, reflex vestibulo-ocular movements preserved — doll's-eye manoeuvre overcomes it) with a nuclear or infranuclear palsy, where reflex movements are also lost. Examiners commonly ask this. Common exam trap: ageing itself restricts upward conjugate gaze, so downgaze limitation, not upgaze limitation, is the meaningful sign in an older patient.

Examiner's Tip — lines that earn marks

Open with: "PSP is a neurodegenerative disorder frequently misdiagnosed as Parkinson's disease, characterised by an extrapyramidal syndrome with complex eye movement dysfunction."

Say "no tremor, axial rigidity, early repeated falls, downgaze palsy, levodopa-unresponsive" as a single string — five marks in one sentence. Describe the MRI precisely: "convex midbrain aspect indicating atrophy, where the normal midbrain aspect is concave." Add the modern framing: "a 4-repeat tauopathy with eight MDS-defined clinical variants." Give subtype-specific prognosis — PSP-RS 5–7 years, PSP-P 8–12 years — and state that death is usually from aspiration pneumonia.