Progressive supranuclear palsy and corticobasal syndrome

01OverviewDefinition, clinical context and the essential points that orientate the chapter.

PSP is a progressive four-repeat tauopathy with clinical variants. The classic Richardson syndrome combines early postural instability and backward falls, axial-predominant rigidity, vertical saccadic slowing progressing to supranuclear gaze palsy and frontal cognitive or behavioural change. Some variants begin with parkinsonism, gait freezing, speech or language impairment, so the diagnostic eye signs and falls may emerge later. Neck extension and a relatively upright rather than flexed posture contrast with typical Parkinson disease, but individual signs are not absolute.

CBS integrates motor and higher cortical dysfunction in one markedly asymmetric limb. The person may describe a hand as useless despite preserved elementary power, cannot perform learned gestures, cannot recognise objects by touch, has stimulus-sensitive myoclonus or feels the limb acts independently. Non-fluent aphasia, visuospatial dysfunction and executive change can later dominate. The label corticobasal syndrome appropriately acknowledges that clinical phenotype cannot reliably predict the exact protein pathology during life.

Diagnosis is specialist and longitudinal. MRI and cognitive or language assessment help exclude alternatives and document supportive patterns; a dopamine-transporter scan may confirm presynaptic deficit but cannot distinguish these degenerative syndromes. Treatment is symptom-specific and multidisciplinary. Falls and visual scanning, limb contracture and pain, communication, drooling, swallowing, mood, cognition, bladder and bowel function and caregiver health need planned review, with goals revisited as progression changes what is achievable.

Key points

Progressive supranuclear palsy is suggested by early unexplained backward falls, axial rigidity, slowing of vertical saccades and later supranuclear vertical gaze palsy, especially downgaze impairment.
The vestibulo-ocular reflex can initially overcome a supranuclear gaze limitation with a doll's-head manoeuvre, distinguishing it from ocular motor-nerve or muscle restriction when safely examined.
PSP commonly adds frontal executive change, apathy or impulsivity, dysarthria, dysphagia, photophobia, blepharospasm and a surprised facial appearance.
Corticobasal syndrome usually begins with markedly asymmetric limb dysfunction combining rigidity, dystonia, myoclonus or bradykinesia with apraxia, cortical sensory loss, alien-limb phenomena or language impairment.
PSP and CBS are clinical syndromes, not guaranteed pathology: PSP syndrome is often a tauopathy, while CBS can result from corticobasal degeneration, Alzheimer pathology, PSP or another process.
Levodopa response is generally limited, but an adequate monitored trial can identify useful symptomatic benefit and should not be judged after one small test dose.
MRI helps exclude stroke, tumour and hydrocephalus and may show midbrain atrophy in PSP or asymmetric cortical atrophy in CBS; supportive patterns are not standalone diagnoses.
Falls, eye-movement limitations, apraxia and impaired insight create distinctive hazards that require occupational, physiotherapy, orthoptic and home assessment early.
Speech and swallowing impairment can progress before patients volunteer difficulty; repeated speech-and-language assessment and anticipatory nutrition discussions are essential.
No medicine reliably stops progression, so honest prognosis, communication support, carer assessment, palliative input and advance-care planning belong alongside active symptom management.

02AetiologyUnderlying causes, associations and risk factors, with why each one matters.

Sporadic tau neurodegeneration

PSP and corticobasal degeneration are usually sporadic disorders involving abnormal tau accumulation, with no single established environmental cause.

Heterogeneous CBS pathology

The clinical corticobasal syndrome can result from corticobasal degeneration, Alzheimer pathology, PSP or another neurodegenerative process.

Rare inherited mimic

A strong family history or unusually young onset should prompt assessment for genetic frontotemporal, parkinsonian or movement disorders rather than presumed sporadic disease.

03PathophysiologyThe causal sequence from the underlying abnormality to symptoms and harm.

1
Tau accumulation
Abnormally modified tau disrupts neuronal and glial microtubules, transport and survival within vulnerable motor and cognitive networks.
2
PSP network degeneration
Midbrain, basal-ganglia and frontal pathway loss causes vertical saccade slowing, axial rigidity, falls, dysphagia and executive change.
3
CBS network degeneration
Asymmetric cortical and basal-ganglia injury produces apraxia, cortical sensory loss, alien-limb phenomena, rigidity, dystonia and myoclonus.
4
Progressive disconnection
Continuing neuronal loss reduces compensation across eye, gait, language, swallowing and limb-control systems as degeneration advances.

04Clinical features and red flagsSymptoms, examination findings, patterns of presentation and time-critical warnings.

PSP Richardson pattern

Within the early course, a person falls backwards without warning, develops axial and neck rigidity, slows vertical saccades and later cannot look down despite preserved vestibulo-ocular reflex.

Frontal and bulbar PSP

Apathy, impulsivity, reduced verbal fluency, emotional lability, strained or slurred speech and dysphagia accompany motor signs and may drive risk more than limb tremor.

CBS asymmetric motor signs

One upper limb becomes stiff, dystonic, jerky and bradykinetic with limited levodopa response, while the opposite side remains much less affected early.

CBS cortical signs

Limb apraxia, cortical sensory loss, impaired graphesthesia or stereognosis, alien-limb behaviour and non-fluent language impairment show cortical network involvement beyond basal-ganglia parkinsonism.

Parkinson disease contrast

A classic rest tremor, clear sustained levodopa response and absence of early falls, gaze, cortical or severe bulbar signs favour idiopathic Parkinson disease, particularly early.

Urgent superimposed illnessRed flag

Abrupt asymmetry, sudden language loss, fever, acute confusion or a step-change in swallowing suggests stroke, infection, seizure or medication harm rather than expected neurodegenerative progression.

05InvestigationsWhat to request, why it matters and how to interpret it.

Investigation order

Read from the initial assessment onwards. Tests may run in parallel in urgent care; first-line, preferred, confirmatory, definitive and gold-standard labels appear only when the chapter explicitly states them.

01
Specialist eye-movement and movement examinationFirst step
Why
Identify saccadic slowing, supranuclear gaze limitation, axial postural instability or the asymmetric cortical-motor combination.
Interpretation and limitations
Test voluntary saccades before range, fixation, convergence and vestibulo-ocular responses, then limb praxis, cortical sensation, myoclonus and alien phenomena. Impaired downgaze has particular functional relevance.
02
MRI brain
Why
Exclude vascular, neoplastic, hydrocephalic and other structural mimics and identify supportive regional atrophy.
Interpretation and limitations
Midbrain atrophy with relative pontine preservation can support PSP; asymmetric frontoparietal atrophy can support CBS. Neither a hummingbird description nor asymmetry proves microscopic pathology.
03
Neuropsychology and speech-language assessment
Why
Define frontal executive, language, praxis, visuospatial, communication and swallowing impairment for diagnosis and care planning.
Interpretation and limitations
Performance can be confounded by gaze palsy, motor slowness and dysarthria. Adapt test presentation so a low score is not simply the consequence of impaired looking or responding.
04
Supervised levodopa trial
Why
Identify useful treatment response and help compare idiopathic Parkinson disease with atypical parkinsonism.
Interpretation and limitations
Assess a tolerated adequate regimen against defined motor and daily-life targets. Some PSP or CBS patients improve partly; a response neither excludes them nor confirms Parkinson disease.
05
Swallow and nutrition evaluation
Why
Detect aspiration, inefficient intake and communication change before pneumonia or severe weight loss occurs.
Interpretation and limitations
Clinical assessment may lead to videofluoroscopy or fibreoptic endoscopic evaluation. Decisions on texture and feeding route integrate aspiration, enjoyment, prognosis and the person's goals.
06
Cause-directed cognitive and motor screen
Why
Exclude treatable metabolic, inflammatory, infectious, medication and structural conditions that can mimic rapid atypical degeneration.
Interpretation and limitations
Use bloods, CSF, EEG, functional imaging or genetic testing only where age, speed, seizures, systemic findings or family history make them informative.

06Differential diagnosisRealistic alternatives and the features that help distinguish them.

Parkinson disease

Asymmetric tremor and sustained levodopa response favour Parkinson disease; early falls, gaze palsy or cortical signs favour PSP or CBS.

Multiple-system atrophy

Severe early autonomic failure, stridor and cerebellar ataxia point towards MSA rather than a primarily gaze or cortical-motor syndrome.

Dementia with Lewy bodies

Early visual hallucinations, cognitive fluctuation and REM sleep behaviour disorder support DLB rather than PSP or CBS.

Stroke or normal-pressure hydrocephalus

Abrupt focal deficits or ventriculomegaly with gait-led urinary-cognitive decline indicates vascular or pressure-related disease rather than steady neurodegeneration.

07ManagementImmediate care, first-line treatment, alternatives and escalation.

01PSP pathwayRecognise gaze and fall chronologyFirst stepAxial parkinsonism is accompanied by early backward falls, visual scanning difficulty or frontal change.

1Map the date of first fall, freezing, speech, swallowing and cognitive change and directly examine vertical saccade velocity, gaze range, vestibulo-ocular response, axial tone and pull response.
2Arrange specialist MRI and movement-disorder assessment, screen injury and bone health and trial levodopa adequately when potential symptomatic benefit justifies it.
3Refer early to physiotherapy, occupational therapy, orthoptics and speech and language therapy for weighted walking advice, environmental modification, visual strategies, communication and swallow planning.
4Review driving and high-risk activities promptly because impaired downgaze and sudden falls can threaten safety before limb weakness is severe.

02CBS pathwayProve cortical-motor integrationA markedly asymmetric stiff or useless limb has apraxia, cortical sensory or alien-limb features.

1Separate elementary weakness, rigidity, dystonia, myoclonus, neglect, sensory loss and praxis by testing each component rather than accepting a general description of clumsiness.
2Use MRI, adapted cognitive and language testing and selected levodopa trial to exclude stroke, tumour and Parkinson disease and to document the syndrome without asserting unproven pathology.
3Treat painful dystonia, myoclonus and contracture while occupational therapy develops one-handed strategies, limb positioning, splints and environmental adaptations.
4Monitor language and swallowing because a motor presentation may evolve into a dominant non-fluent aphasia or bulbar disability.

03Progressive supportPrevent predictable complicationsFalls, dysphagia, communication failure, immobility or caregiver dependency is increasing.

1Investigate sudden decline for infection, injury, constipation, retention, pain and medicine effects before attributing it to the underlying disease.
2Repeat swallowing and nutrition assessment, prescribe communication aids before speech is lost and address saliva without creating unmanageable dry, thick secretions.
3Coordinate equipment, wheelchair and transfer plans, pressure and thrombosis prevention, continence, mood, cognition, social care, benefits and respite support.
4Introduce palliative and advance-care discussions according to need and preference, including aspiration treatment, feeding, hospital transfer and place-of-care wishes.

Key medicines and prescribing safety5 treatments · regimens, roles and cautions

May give modest benefit in a PSP-parkinsonism variant or selected CBS despite typical limited responsiveness.

Levodopa combination therapy

Use an adequate specialist-supervised trial titrated to gait, rigidity and meaningful daily activities.

Monitor postural hypotension, hallucinations, nausea and dyskinesia; taper if ineffective rather than stopping suddenly, and do not let a partial response erase cortical or gaze signs.

Can reduce focal painful dystonia, blepharospasm or selected secretion problems and facilitate care or positioning.

Botulinum toxin type A

An expert injector selects muscles and dose at intervals usually around twelve weeks by product.

Local weakness can worsen head control or swallowing, products are not dose-equivalent and injection goals and response should be documented each cycle.

May reduce jerks that impair function, sleep or safe care in corticobasal syndrome.

Clonazepam or levetiracetam

Begin cautiously at a low specialist-selected dose and titrate only against disabling myoclonus.

Sedation, falls, behavioural effects and swallowing risk can exceed benefit; avoid broad treatment of every small movement without a functional target.

Treats depression or anxiety and may improve engagement and quality of life despite ongoing neurodegeneration.

Antidepressant therapy

Select and titrate a formulary agent according to mood, anxiety, sleep, pain and comorbidity.

Differentiate apathy from depression, review falls, sodium, bleeding and serotonergic interactions, and combine medicine with psychological and caregiver support.

Reduces socially and physically troublesome drooling caused by impaired automatic swallowing rather than excess production.

Saliva management

Start with posture and swallow strategies; use locally commissioned antimuscarinic or botulinum treatment cautiously.

Dry mouth, thick secretions, dental disease, constipation, urinary retention, confusion and worsened swallowing may result, especially from systemic anticholinergic burden.

08ComplicationsImportant consequences, why they occur and why they matter clinically.

Falls and fractures

Early postural instability, gaze limitation and impaired judgement cause repeated backward falls, injury and rapid mobility loss.

Dysphagia and aspiration

Swallowing impairment progresses early, producing choking, pneumonia, weight loss and difficult nutrition decisions as disease advances.

Communication and cognitive loss

Dysarthria, language dysfunction, executive change and apraxia reduce communication, capacity and ability to use aids independently.

Contracture and care dependence

Rigidity, dystonia and asymmetric limb dysfunction cause pain, skin, hygiene and transfer problems that increasingly burden carers.

09Monitoring and follow-upTreatment response, safety checks and longer-term review.

Track falls, near-falls, head injuries, pull response, transfers, wheelchair use and visual scanning at each review, with rapid equipment adjustment as function changes.
Repeat vertical saccade, gaze, speech, praxis, cortical sensation, language and cognitive assessment so syndrome evolution informs diagnosis and support.
Measure weight, meal duration, cough, chest infections, saliva, voice and swallowing safety; reassess instrumentally when recommendations or goals may change.
Review pain, dystonia, myoclonus, contracture, skin, sleep, continence and bone health, checking that symptom medicines have produced functional rather than merely numerical benefit.
Assess communication access, decision-making support, mood, carer strain, home safety, social care and advance plans before crises remove the opportunity for choice.
Safety-net abrupt deficit, acute confusion, fever, trauma, choking and rapid loss of mobility for urgent assessment of a superimposed treatable problem.

10Special situationsVariants, exceptions and circumstances that change the usual approach.

Supranuclear means bypassable

Early voluntary downgaze may fail while vestibular head movement still drives the eyes, localising dysfunction above the ocular motor nuclei.

CBS is a syndrome

The striking asymmetric cortical-motor phenotype does not guarantee corticobasal degeneration pathology, so language should preserve uncertainty during life.

Apraxia is not weakness

A person may have enough power yet cannot execute a learned gesture; testing comprehension, sensation and elementary movement prevents misclassification.

Falls can precede tremor

Repeated backward falls early in an axial syndrome are much more diagnostically useful for PSP than waiting for a classic limb rest tremor.

Eye signs affect testing

Reading and visually presented cognitive tasks can underestimate ability when downgaze and saccades are impaired, so assessments need adaptation.

Feeding is a values decision

A tube may support nutrition but does not eliminate aspiration from saliva or reflux; goals, burdens and disease trajectory require explicit discussion.

11Common pitfallsFrequent interpretation and management errors.

01
Calling every patient with early falls Parkinson disease without examining vertical saccades and axial rigidity.
02
Diagnosing corticobasal degeneration pathology solely from an asymmetric clinical corticobasal syndrome.
03
Misinterpreting limb apraxia as weakness because power, cortical sensation and learned movement were not separately tested.
04
Using one small levodopa dose to declare permanent non-response in either syndrome.
05
Waiting for aspiration pneumonia before arranging speech, swallowing, nutrition and communication assessment.
06
Attributing an abrupt focal or cognitive deterioration to progression and missing stroke, infection, trauma or medication toxicity.