21st June 2023

Parkinson’s Plus Syndromes

Progressive Supranuclear Palsy

Progressive supranuclear palsy (PSP) is caused by two pathological processes:

1. Neuronal loss in:
   • Midbrain – supranuclear gaze palsies
   • Basal ganglia – parkinsonism
   • Cortex – cognitive deficits
2. Tau inclusions

The cardinal features of PSP are:

• Supranuclear ophthalmoplegia
• Neck dystonia – backward tilt of the head
• Parkinsonism
• Pseudobulbar palsy
• Cognitive impairment
• Imbalance – axial rigidity, erect posture
• Fast walking
• Frequent falls backwards

Supranuclear ophthalmoplegia classically causes a downgaze palsy as well as square wave jerks when moving their eyes. The supranuclear ophthalmoplegia is due to an upper motor neuron problem of the extraocular muscles and is distinguished from a lower motor neuron problem with a negative doll’s eyes reflex. Patients struggle with the H test and have square wave jerks when moving their eyes.

MRI head – classic “hummingbird sign” – atrophy of midbrain, preservation of pons.

Later symptoms of PSP are:

• Spastic-ataxic dysarthria
• Dysphagia
• Falls
• Dementia

Treatment for PSP includes:

• Levodopa – will have only a brief beneficial effect
• Amantadine can help motor features
• Botulinum toxin A – neck dystonia and blepharospasm
• Often given a forward weighted walker, as they have a tendency to fall backwards.

Multi-system Atrophy

Multi-system atrophy (MSA) is caused by progressive neuronal loss in the substantia nigra, striatum, cerebellum, and autonomic nervous system.

The histopathologic hallmark of MSA is Papp-Lantos bodies of α-synuclein and ubiquitin.

The most common first sign of MSA is an “akinetic-rigid syndrome”.

MSA commonly presents as a triad of:

1. Parkinsonism
2. Ataxia
3. Autonomic dysfunction

There are two types of MSA:

1. MSA-P – predominantly parkinsonism. MRI head – hypodense putamen.
2. MSA-C – predominantly cerebellar – ataxia, dysphagia, and dysarthria. MRI head – “hot cross bun sign” – atrophy of the cerebellum, pons and pontocerebellar fibres.

Similarly to PSP, patients with MSA can sometimes briefly benefit from levodopa.

The postural hypotension can be treated with the following:

• Conservative management, such as compression stockings or additional salt
• Fludrocortisone or midodrine

Bladder issues can be managed with oxybutynin or tolterodine. Dystonia and contractures can be managed with physiotherapy or, in refractory cases, with botulinum toxin A.

Corticobasal Degeneration

Corticobasal degeneration (CBD) causes neurodegeneration in:

• Premotor cortex
• Parietal association areas
• White matter tracts
• Thalamus
• Basal ganglia

This is caused by astroglial tau inclusions in the anterior frontal lobe and the premotor area.

CBD presents with the following:

• Progressive asymmetric axial rigidity
• Abnormal hand or foot postures
• Parkinsonism

It commonly causes a clumsy hand due to apraxia, bradykinesia, akinetic rigidity and dystonia. A specific presentation of CBD is alien hand syndrome, a phenomenon presenting as a hand that moves on its own, in reaction to external stimuli, without control, and the hand feels foreign to the patient.

Patients with CBD also have the following:

• Ideomotor apraxia – unable to repeat or mimic particular movements. This makes the initiation of walking difficult, as their foot appears fixed to the floor.
• Non-fluent dysphasia/aphasia – disconnected speech and omission of words, which progresses to aphasia.

As CBD progresses, the symptoms become bilateral, and patients can develop frontotemporal dementia.

The diagnosis of CBD is usually a clinical one. However, the imaging modalities that can aid diagnosis include:

• MRI head – posterior parietal and frontal atrophy with atrophy of the corpus callosum.
• SPECT imaging – hypoperfusion in the posterior regions of the frontal and parietal lobes.

Levodopa has a limited effect in CBD. For painful stiffness, myoclonus, contractures, or dystonia, the treatments are:

• Regular splinting
• Clonazepam
• Baclofen
• Botulinum toxin A injections
• Intensive PT