From the Guidelines
Progressive supranuclear palsy (PSP) is a rare neurodegenerative brain disorder characterized by the gradual deterioration of brain cells in areas controlling eye movements, balance, and other motor functions, with a prevalence of around 5/100,000 1. PSP is also known as Steele-Richardson-Olszewski syndrome, and patients classically present in the sixth or seventh decade (mean age of onset at 63) with a lurching gait and axial dystonia, manifested as unexplained falls 1. The clinical presentation of PSP includes:
- Ocular symptoms, such as blurred vision and slow saccades, which can be seen early in the disease
- Vertical supranuclear gaze palsy, usually only seen later in the course of the disease
- Frequent falls, stiffness, slow movements, slurred speech, difficulty swallowing, and changes in personality or cognition PSP is caused by the abnormal accumulation of tau protein in brain cells, forming tangles that damage neurons 1. The condition usually affects people over 60 and progresses over time, with most patients requiring significant care within 3-5 years of diagnosis. Currently, there is no cure for PSP, and treatment focuses on managing symptoms with medications and therapy 1. Key aspects of PSP diagnosis and management include:
- Correctly diagnosing a Parkinsonian syndrome on clinical features alone can be quite challenging, and imaging remains an essential diagnostic tool in the evaluation of a patient presenting with Parkinsonian symptoms 1
- PSP is often misdiagnosed as Parkinson's disease initially but differs in its poor response to Parkinson's medications and more rapid progression 1
From the Research
Definition and Characteristics of Progressive Supranuclear Palsy
- Progressive supranuclear palsy (PSP) is a complex clinicopathologic disease with no current cure or disease-modulating therapies that can only be definitively confirmed at autopsy 2.
- PSP is a tauopathy with a relentless course, usually starting in the mid-60s and leading to death after an average of 7 years 3.
- Clinical deficits in PSP are numerous, involve the entire neuraxis, and present as several discrete phenotypes, including rigidity, bradykinesia, postural instability, gait freezing, supranuclear ocular motor impairment, dysarthria, dysphagia, incontinence, sleep disorders, frontal cognitive dysfunction, and a variety of behavioral changes 3.
Diagnosis and Treatment of Progressive Supranuclear Palsy
- The 2017 International Parkinson and Movement Disorder Society PSP criteria outline 14 core clinical features and 4 clinical clues that combine to diagnose one of eight PSP phenotypes with probable, possible, or suggestive certainty 4.
- Current standard-of-care treatment of PSP is multidisciplinary, supportive, and symptomatic, with several trials of potentially disease-modulating agents having been completed with disappointing results 2.
- Low-dose amitriptyline may improve severe motor dysfunction in PSP significantly, but dosing must be individualized for optimal response and minimal toxicity 5.
- Botulinum toxin-A can improve muscle rigidity in the upper limbs of patients with PSP 6.
Research and Clinical Trials
- Growing understanding of the phenotypic diversity of PSP has led to expanded clinical criteria and new insights into etiopathogenesis, making increased access to current clinical trials possible 2.
- Current ongoing clinical trials target the abnormal aggregation of tau through a variety of mechanisms, including immunotherapy and gene therapy, offering a more direct method of treatment 2.
- Newly expanded clinical criteria and improved specific biomarkers will aid in identifying patients with PSP earlier and more accurately, expanding access to potentially beneficial clinical trials 2.