NeurologyTier 1Disease (DEADMAN)

Parkinson disease and related conditions - corticobasal degeneration

Description

4-repeat tauopathy producing a strikingly asymmetric akinetic-rigid syndrome with cortical signs
Separate the words: corticobasal syndrome (CBS) = the clinical picture; corticobasal degeneration (CBD) = the pathology
- Only ~25-50% of CBS turns out to be CBD at autopsy - the rest are PSP, Alzheimer, FTLD-TDP, CJD
- CBD pathology equally often presents as something other than CBS (PSP-like, frontal behavioural, non-fluent aphasia)

Core clinical features

Basal ganglia ("basal")

Markedly asymmetric rigidity and akinesia - "my arm stopped working"
Limb dystonia - fixed flexed, adducted posture
Focal reflex myoclonus - jerks on touch or stretch, superimposed on the dystonic limb
Levodopa-unresponsive

Cortical ("cortico")

Limb apraxia - ideomotor, the most characteristic cortical sign
Cortical sensory loss - agraphaesthesia, astereognosis, impaired two-point discrimination, extinction (with normal primary modalities)
Alien limb phenomenon - the limb acts with apparent purpose, levitates, or interferes with the other hand; patient disowns it
Non-fluent/agrammatic aphasia, apraxia of speech (dominant hemisphere)
Frontal behavioural change, executive dysfunction

Dementia occurs and may be the presentation, but is not part of the core criteria
Later: gait disorder, falls, dysphagia, oculomotor apraxia (difficulty initiating saccades with normal range - contrast PSP's restricted range)

Epidemiology

Rare: incidence ~0.6-0.9 per 100,000/yr, prevalence ~5-7 per 100,000
~4-6% of parkinsonism
Onset typically 60-70 yrs; onset under 45 is very unusual and should prompt reconsideration
M = F (slight F predominance in some series)
Almost always sporadic; MAPT H1 haplotype over-represented, as in PSP

Aetiopathogenesis

4R tau deposition -> neuronal and glial inclusions
- Astrocytic plaques are the pathological hallmark (vs tufted astrocytes in PSP - the key distinguishing lesion)
- Ballooned achromatic neurons, threads in grey and white matter
Asymmetric atrophy of the perirolandic frontoparietal cortex + substantia nigra + basal ganglia
- Cortical involvement explains apraxia, cortical sensory loss and alien limb; nigral and striatal involvement explains the rigidity
Postsynaptic striatal degeneration -> levodopa-unresponsive
MAPT H1/H1 genotype; rare MAPT and PGRN mutation-associated cases

Causes of a corticobasal SYNDROME

Always re-derive the pathology from the clinical picture - this is where the exam lives.

Corticobasal degeneration (~25-50%)
Progressive supranuclear palsy (PSP-CBS)
Alzheimer disease (particularly with early onset, episodic memory loss, posterior atrophy) - amyloid PET / CSF changes management
FTLD-TDP (including C9orf72, progranulin)
Creutzfeldt-Jakob disease - rapid course, myoclonus; do a DWI MRI and consider RT-QuIC if the tempo is weeks-months
Structural: parasagittal meningioma, stroke; anti-IgLON5; Whipple

Diagnosis

Clinical; definitive diagnosis requires neuropathology. Armstrong criteria define probable/possible CBD.

The clinical combination

Asymmetric presentation of >=2 of: akinetic-rigid limb, limb dystonia, limb myoclonus
PLUS >=2 of: orobuccal or limb apraxia, cortical sensory deficit, alien limb
Insidious onset, gradual progression, >=1 year duration, age >=50
Exclusions: Lewy body disease features, classical levodopa response, prominent early autonomic failure, semantic/logopenic aphasia, focal structural lesion

Examination sequence

Compare sides deliberately - asymmetry is the diagnosis
Tone: rigidity, dystonic posturing; attempt to open the fisted hand
Test apraxia: "show me how you would use a comb / blow out a match / salute" - with each hand separately, then imitation, then with the real object
Cortical sensation: graphaesthesia, stereognosis, two-point, double simultaneous stimulation for extinction - with primary modalities intact
Provoke myoclonus: tap, stretch, light touch of the fingers
Watch for alien limb during history-taking, not on command
Frontal signs, verbal fluency, speech apraxia
Eye movements: slowed initiation of saccades with preserved range (oculomotor apraxia)
Postural stability, gait

Investigations

MRI brain - asymmetric perirolandic frontoparietal atrophy, contralateral to the affected limb; excludes structural mimics
FDG-PET - asymmetric frontoparietal and basal ganglia hypometabolism
Amyloid PET or CSF Abeta42/p-tau ratio - the single most useful adjunct: identifies the Alzheimer subgroup of CBS, who may respond differently and whose prognosis and counselling differ
DAT scan - asymmetric reduction; does not distinguish from PD or PSP
Neuropsychology - dissociated apraxia, executive and visuospatial deficits
If rapid (weeks-months): DWI MRI, EEG, CSF RT-QuIC for CJD
Consider genetic testing (MAPT, GRN, C9orf72) if family history or early onset

Management

No disease-modifying therapy. Symptom-directed and multidisciplinary; benefits are modest but real.

A. By symptom

Problem	Approach
Rigidity/akinesia	Levodopa trial to a genuine dose - only a minority get modest, transient benefit. Withdraw if no response
Limb dystonia	Botulinum toxin - the most effective single intervention; prevents painful contracture and skin maceration in a fisted hand
Myoclonus	Clonazepam first; levetiracetam or valproate as alternatives
Apraxia	No drug. OT compensatory strategies, task simplification, one-handed equipment
Alien limb	No drug. Sensory tricks, keeping the limb occupied (holding an object), safety measures
Pain	Common and under-treated - dystonia, contracture, frozen shoulder; treat the dystonia
Depression/apathy	SSRI; pseudobulbar affect responds to SSRI
Speech/swallow	Early speech pathology; communication aids while comprehension is preserved

B. Multidisciplinary and anticipatory

Physiotherapy - maintain range, prevent contracture, gait and falls training
Occupational therapy - home modification, splinting, adaptive equipment; the highest-yield discipline in CBD
Falls prevention, hip protectors
Nutrition - videofluoroscopy, texture modification; PEG discussion early
Advance care planning while communication and capacity permit - progressive aphasia makes later discussion impossible
Carer support, respite, and financial/NDIS or My Aged Care pathways
Driving cessation - apraxia, alien limb and asymmetric rigidity make this early and non-negotiable
Brain donation discussion - the only route to a definitive diagnosis

Avoid

Dopamine agonists - confusion, hallucination, no benefit
Anticholinergics - worsen cognition
Antipsychotics where avoidable
Prolonged escalating levodopa in a clearly unresponsive patient

Associations

Progressive supranuclear palsy - shared 4R tau pathology, overlapping phenotypes, both MAPT H1
Frontotemporal dementia spectrum - non-fluent variant primary progressive aphasia, behavioural variant
Alzheimer disease - a common pathological substrate of corticobasal syndrome
Motor neurone disease overlap (rare, C9orf72)
Argyrophilic grain disease, globular glial tauopathy
Depression, apathy, pseudobulbar affect
Contracture, pressure injury, chronic pain
Autonomic failure and REM sleep behaviour disorder are NOT features - their presence points to a synucleinopathy

Natural history & complications

Begins in one limb, spreads to the ipsilateral limb, then contralaterally over ~2-5 years
Median survival ~6-8 years from onset (range 2-12)
Progression to wheelchair dependence, anarthria and dysphagia
Early bilateral involvement, early frontal/cognitive features and early dysphagia predict shorter survival
Aspiration pneumonia is the usual cause of death

Complications

Painful fixed dystonic contracture, skin breakdown in the clenched hand
Falls, fracture, subdural haematoma
Aspiration pneumonia, malnutrition, weight loss
Anarthria - loss of all communication while comprehension may be relatively preserved (a major source of distress; act on it early)
Immobility - pressure injury, VTE, contracture
Severe carer burden

Contrast with the other atypical parkinsonian syndromes

	CBD	PSP	MSA
Symmetry	Markedly asymmetric	Symmetric	Symmetric
Signature	Apraxia, alien limb, cortical sensory loss, focal reflex myoclonus	Early backward falls, vertical supranuclear gaze palsy	Autonomic failure, cerebellar signs
Eye movements	Slow saccade initiation, range preserved	Restricted vertical range, downgaze first	Nystagmus, saccadic pursuit
MRI	Asymmetric frontoparietal atrophy	Hummingbird sign	Hot cross bun, putaminal rim
Pathology	4R tau - astrocytic plaques	4R tau - tufted astrocytes	alpha-synuclein - glial cytoplasmic inclusions

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