This is an interesting article by perhaps the top two PSP researchers in the world — Lees of the old guard and Williams of the new guard.
When looking at the brains of those with a pathological diagnosis of progressive supranuclear palsy (PSP), there are some differences:
(a) in the severity of pathology in the brain,
(b) in the distribution of pathology in the brain, and
(c) clinical features
Presumably three of the disease “subgroups” the authors refer to include: Richardson’s Syndrome (described elsewhere as “classic PSP”), PSP-Parkinsonism, and primary progressive freezing gait (PPFG). I’m unclear if “pure akinesia with gait freezing” (PAGF) is another PSP subgroup or not. (Or if it’s the new name for PPFG. So many acronyms!)
This review article addresses these differences. You’ll have to check out the full article to see all the differences. In this post, I’m only sharing the differences in “clinical features” or symptoms.
The authors describe five clinical subgroups or types of PSP:
#1- Richardson’s syndrome (“classic PSP”)
Symptoms include: 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; slow, slurred, growling speech; swallowing difficulties; overactivity of the frontalis; surprised, worried facial appearance; muscle tone can be normal; acoustic startle response absent in most patients; auditory blink reflex absent in most patients.
“The median survival in the original series was 5 years from disease onset; in larger, more recent studies, disease durations to death of 5 to 8 years have been reported.”
#2- PSP-Parkinsonism (PSP-P)
Symptoms include: limb bradykinesia; limb rigidity is more common and severe than in patients with Richardson’s syndrome; jerky postural tremor; 4-6 Hz rest tremor; asymmetry of limb signs in some cases; axial rigidity; “moderate or good improvement in bradykinesia and rigidity” following levodopa therapy, “although the response is rarely excellent”; acoustic startle response absent in most patients; auditory blink reflex preserved in all patients.
Those with PSP-P are “commonly misdiagnosed with Parkinson’s disease.”
“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.”
PSP-P compared to other disorders:
(a) “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.”
(b) auditory blink reflex “was absent in most patients with Richardson’s syndrome but was preserved in all patients with PSP-P”
(c) “[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…”
“In a few patients, a purely parkinsonian syndrome predominates until death, and abnormalities of eye movement or other characteristics of Richardson’s syndrome might never appear. A sustained response to levodopa and drug-induced choreic dyskinesias with a long duration of disease seem to characterise these patients.”
The prevalence of the PSP-P type seems to be between 8% and 32% of those with PSP pathology.
#3 – PSP-Pure akinesia with gait freezing (PSP-PAGF)
Symptoms include: “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; acoustic startle response present in all patients; 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.”
“The median duration of disease was 11 years.”
Fewer than 1% have this type of PSP.
#4- PSP-Corticobasal syndrome (PSP-CBS)
Symptoms include: asymmetric limb dystonia; apraxia; alien limb. “An 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. The distinction between this and the typical slowness of saccadic eye movements in Richardson’s syndrome can be difficult to make early in the course of the disease.”
“Most patients with PSP-CBS eventually develop postural instability but this occurs much later in Richardson’s syndrome.”
“Pathological series have indicated that only 50% of patients with CBS have pathology that is typical of corticobasal degeneration… Cerebrovascular disease, Alzheimer’s disease, and progressive supranuclear pathology account for most of the other patients.”
“PSP-CBS seems to be 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.”
#5- Progressive non-fluent aphasia (PNFA)
Symptoms include: non-fluent spontaneous speech, with hesitancy; agrammatism; “phonemic errors that require substantial effort in speech production.”
“In a small case series, five of seven patients who presented with PNFA and prominent early apraxia of speech had underlying PSP-tau pathology. The other two patients had Pick’s disease and corticobasal degeneration… The apparent specificity of prominent early apraxia of speech for tauopathies, particularly PSP-tau pathology, has [led] to the suggestion that this syndrome should be regarded as a clinical subtype of PSP. Patients who present with prominent early apraxia of speech do so at similar ages of onset or disease duration as patients with Richardson’s syndrome.”
Conclusions. In the conclusion to the review article, the authors state:
“The early recognition of patients with Richardson’s syndrome, PSP-P, PSP-CBS, PAGF, or PSP-PNFA would be enhanced by biomarkers for tauopathies and clinical criteria with a high positive predictive value for Parkinson’s disease, which is the main differential diagnosis for these conditions and is 30 times more prevalent than PSP.”
And:
“Clinical features, such as visual hallucinations, drug-induced dyskinesias, hyposmia, and a prolonged sustained response to levodopa are uncommon in PSP, but have not yet been prospectively assessed in PSP-P, PAGF, or PSP-CBS.”
This sentence of the abstract is important, given that it is in conflict with the “typical”(?) patient’s desire to have a diagnosis:
“[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.”
Copied below is the abstract.
Robin
Lancet Neurology. 2009 Mar;8(3):270-9.
Progressive supranuclear palsy: clinicopathological concepts and diagnostic challenges.
Williams DR, Lees AJ.
Faculty of Medicine (Neurosciences), Monash University, Melbourne, Australia; Reta Lila Weston Institute of Neurological Studies, University College London, London, UK.
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.
PubMed ID#: 19233037 (see pubmed.gov for this abstract)