Brain Matters

"Progressive supranuclear palsy: clinicopathological concepts and diagnostic challenges"

Lancet Neurology. 2009 Mar;8(3):270-9.

Williams DR, Lees AJ.
Faculty of Medicine (Neurosciences), Monash University, Melbourne, Australia; Reta Lila Weston Institute of Neurological Studies, University College London, London, UK.

PubMed ID#: 19233037

This recent article describes the two most common types of PSP along with three other, less common types.

Five Clinical Types of PSP

The authors describe five clinical types of PSP:

Richardson's syndrome (RS)
* lurching gait; postural instability; unexplained backwards falls;
* personality change;
* cognitive decline;
* slowing of vertical saccadic eye movements ("an early telltale sign"); eyelid abnormalities; severely impaired spontaneous blink rate; auditory blink reflex absent in most patients;
* slow, slurred, growling speech; swallowing difficulties;
* overactivity of the frontalis; surprised, worried facial appearance;
* median survival time after disease onset is 5 years (initial study) or 5 to 8 years (more recent studies)

PSP-Parkinsonism (PSP-P)
* limb bradykinesia; limb rigidity is more common and severe than in patients with Richardson's syndrome;
* moderate or good improvement in bradykinesia and rigidity following levodopa therapy, "although the response is rarely excellent"
* jerky postural tremor; 4-6 Hz rest tremor
* asymmetry of limb signs in some cases
* axial rigidity
* auditory blink reflex preserved in all patients
* commonly misdiagnosed with Parkinson's disease
* "A sustained response to levodopa and drug-induced choreic dyskinesias with a long duration of disease seem to characterise these patients."
* "Falls and cognitive dysfunction occur later in PSP-P than they do in Richardson's syndrome and, perhaps as a consequence, the time for disease duration to death is about 3 years longer in PSP-P."
* prevalence seems to be between 8% and 32% of those with PSP pathology

PSP-P compared to RS:

• "PSP-P and Richardson's syndrome can be distinguished by their different clinical pictures in the first 2 years; however, there is clinical overlap, and after 6 years of follow up the clinical phenomenology might become similar."

• "In a few patients...abnormalities of eye movement or other characteristics of Richardson's syndrome might never appear."

PSP-P compared to PD:

• "[We] emphasize the difficulty in separating these [PSP-P] patients from those with [PD]. Early pointers that might help a clinical diagnosis of PSP-P could include rapid progression, prominent axial symptomatology, or a poor response to levodopa..."

PSP-Pure akinesia with gait freezing (PSP-PAGF)
* "progressive onset of gait disturbance with start hesitation and subsequent freezing of gait, speech, or writing"
* "without rigidity, tremor, dementia, or eye movement abnormality during the first 5 years of the disease"
* no benefit to levodopa therapy
* auditory blink reflex preserved in all patients
* PAGF was "first described in 1974 in two patients who developed freezing of gait, writing, and speech, with paradoxical kinesia. At presentation, these patients were cognitively intact, had no abnormalities of eye movement, and, as is the case in many patients, there was a long disease duration without the development of other parkinsonian features."
* median disease duration is 11 years
* fewer than 1% have this type of PSP

PSP-Corticobasal syndrome (PSP-CBS)
* asymmetric limb dystonia
* apraxia
* alien limb
* "increase in latency to initiate saccadic eye movements, which leads eventually to compensatory head tilts, is the most common eye movement abnormality and is typically more pronounced on the side on which the apraxia predominates."
* a rare presentation of PSP-tau pathology:  "only five patients from a pathological series of 160 patients with PSP was identified with asymmetric limb dystonia, apraxia, and alien limb phenomena."

PSP-CBS compared to RS:

• In PSP-CBS, there is an "increase in latency to initiate saccadic eye movements" while in RS there is a "typical slowness of saccadic eye movements."  This distinction can be difficult to identify early on.

• Postural instability occurs much in PSP-CBS than in RS.

Progressive non-fluent aphasia (PNFA)
* non-fluent spontaneous speech, with hesitancy
* agrammatism
* "phonemic errors that require substantial effort in speech production"
* prominent early apraxia of speech, which is specific to tauopathies, particularly PSP-tau pathology

Abstract

Here's the full abstract for this article:  (we've added the paragraph breaks)

"Progressive supranuclear palsy (PSP) is a clinical syndrome comprising supranuclear palsy, postural instability, and mild dementia. Neuropathologically, PSP is defined by the accumulation of neurofibrillary tangles. Since the first description of PSP in 1963, several distinct clinical syndromes have been described that are associated with PSP; this discovery challenges the traditional clinicopathological definition and complicates diagnosis in the absence of a reliable, disease-specific biomarker.

We review the emerging nosology in this field and contrast the clinical and pathological characteristics of the different disease subgroups. These new insights emphasise that the pathological events and processes that lead to the accumulation of phosphorylated tau protein in the brain are best considered as dynamic processes that can develop at different rates, leading to different clinical phenomena.

Moreover, for patients for whom the diagnosis is unclear, clinicians must continue to describe accurately the clinical picture of each individual, rather than label them with inaccurate diagnostic categories, such as atypical parkinsonism or PSP mimics. In this way, the development of the clinical features can be informative in assigning less common nosological categories that give clues to the underlying pathology and an understanding of the expected clinical course."