Psp diagnostic program

Thus, early and reliable diagnosis of PSP remains a major clinical challenge, but is justifiably demanded by patients and their carers and is highly important for estimation of prognosis, appropriate allocation to therapeutic trials, and development of new diagnostic tools. In brief, the steering committee G.

Study group members were encouraged to add relevant articles to be considered throughout the project period end of , particularly those published after The literature was analyzed following the Scottish Intercollegiate Guidelines Network recommendations. The literature-based evidence was then summarized by the working groups for imaging and clinical aspects and is published in detail in accompanying papers in this issue of Movement Disorders. These data were used to estimate and stratify the diagnostic value of the clinical items selected from a comprehensive literature review and are reported in detail in an accompanying paper.

Third, on the basis of the evidence obtained in the first two steps, the steering committee drafted an initial proposal of the criteria, which was distributed to the MDS-PSP study group members. They provided written feedback to the process coordinator G. In March , the group convened for a 2-day consensus meeting in Munich to present and discuss all aspects of the criteria structure, basic features, exclusion criteria, core functional domains, operationalized clinical features, supportive findings, imaging, biomarkers, and genetics.

For each of these items, the data obtained in the first two steps were presented by the subgroup coordinators. Thereafter, the written draft of the criteria was discussed stepwise. Modifications were integrated until the entire group unanimously agreed to the items under discussion.

After the meeting, the written document was circulated again and optimized in three further Delphi rounds, in particular, dealing with precise wording, operationalized definition of clinical examination guidelines, and newly evolving aspects, such as tau PET imaging. After final approval, the current manuscript was written G. Basic features need to be present in a patient in order to be considered for the diagnosis of PSP of any phenotype and at any stage Table 1.

Mandatory inclusion criteria Table 1, B1 indicate the presence of a sporadic, adult-onset, gradually progressive neurodegenerative disease. Context-dependent exclusion criteria Table 1, B3 also rule out PSP, but should be applied only in patients presenting with suggestive, unusual clinical features justifying further investigation. Predominant, otherwise unexplained autonomic failure, e. Predominant, otherwise unexplained visual hallucinations or fluctuations in alertness, suggestive of dementia with Lewy bodies.

Predominant, otherwise unexplained multisegmental upper and lower motor neuron signs, suggestive of motor neuron disease pure upper motor neuron signs are not an exclusion criterion. Sudden onset or step-wise or rapid progression of symptoms, in conjunction with corresponding imaging or laboratory findings, suggestive of vascular etiology, autoimmune encephalitis, metabolic encephalopathies, or prion disease. Identifiable cause of postural instability, e. Relevant structural abnormality, e.

In cases with very rapid progression, exclude cortical and subcortical hyperintensities on DWI-MRI suggestive of prion disease. Niemann-Pick disease, type C e. Prion disease e. In patients with suggestive features i.

MAPT rare variants mutations are no exclusion criterion, but their presence defines inherited, as opposed to sporadic PSP. MAPT H2 haplotype homozygosity is not an exclusion criterion, but renders the diagnosis unlikely. LRRK2 and Parkin rare variants have been observed in patients with autopsy confirmed PSP, but their causal relationship is unclear so far. Known rare variants in other genes are exclusion criteria, because they may mimic aspects of PSP clinically, but differ neuropathologically; these include.

Non- MAPT associated frontotemporal dementia e. We propose four core functional domains as characteristic clinical manifestations of PSP ocular motor dysfunction [O], postural instability [P], akinesia [A], and cognitive dysfunction [C]; Table 2.

In each domain, we propose three characteristic core clinical features, stratified by presumed levels of certainty 1 [highest], 2 [mid], and 3 [lowest] that they contribute to the diagnosis of PSP Table 2. Levels with lower numbers are considered to contribute higher certainty to a diagnosis of PSP than levels with higher numbers.

Operationalized definitions of the core clinical features are provided in Table 4. Supportive features Table 3 are those having positive predictive values insufficient to qualify them as diagnostic features, but sufficient to provide helpful ancillary evidence to increase informal diagnostic confidence.

The core clinical features, supportive clinical clues, and supportive imaging findings were operationalized in an attempt to standardize the application of the MDS-PSP criteria Table 4. Operationalized definitions of core clinical features, supportive clinical clues, and supportive imaging findings. Four levels of diagnostic certainty are proposed Table 5. Definite PSP is the neuropathological gold standard defining the disease entity, regardless of its clinical presentation.

Probable PSP is diagnosed in the presence of a combination of clinical features with high specificity. Possible PSP is diagnosed in the presence of clinical features considered to substantially increase the sensitivity for PSP. Clinical syndromes suggestive of PSP have features that alone or in combination may constitute early, subtle evidence for PSP with modest, but still useful, positive predictive value.

Additional presence of imaging findings IF1 or IF2 qualifies for the label imaging supported diagnosis. Degrees of diagnostic certainty, obtained by combinations of clinical features and clinical clues.

Core clinical features are defined by their functional domain ocular motor dysfunction [O], postural instability [P], akinesia [A], and cognitive dysfunction [C] , and stratified by presumed levels of certainty 1 [highest], 2 [mid], 3 [lowest] they contribute to the diagnosis of PSP see Table 2. Supportive clinical clues CC are presented in Table 3.

Operationalized definitions of clinical features and clinical clues are given in Table 4. Clinical predominance types are determined based on the combination of clinical features Table 5.

Here, we propose new MDS-PSP criteria, which are aimed to optimize early, sensitive, and specific clinical diagnosis of PSP on the basis of currently available evidence.

They are intended for use in both clinical practice and research, including the diagnosis of early and variant PSP for clinical trials. The new diagnostic criteria accept the neuropathological examination as the gold standard to define PSP as a disease entity. We still consider PSP as a sporadic, not as a monogenic disease, because clinical or pathological phenocopies resulting from rare genetic variants mutations in MAPT do not share an identical etiology to sporadic PSP.

Because sporadic occurrence does not ultimately rule out underlying monogenic inheritance, particularly in small families, MAPT sequencing may be considered, where higher certainty is warranted. We continue to set the minimum age at onset as 40, given that no autopsy-confirmed case has been demonstrated to manifest earlier, whereas some PSP look-alikes e. We also specified the onset of PSP-related symptoms as including neurological, cognitive, or behavioral deficits to reflect current knowledge of the broad clinical spectrum over which PSP may range.

Inclusion and exclusion criteria have been carefully adapted to the current state of knowledge, as presented in accompanying papers. This accounts for the results obtained by hypothesis-free cluster analyses in two independent large clinicopathological series of definite PSP patients, identifying these four domains as most representative of characteristic disease manifestations.

These were identified through the systematic literature review, validated quantitatively in the clinicopathological cohort, and specified where required by expert consensus. Of note, these levels may coincide with a typical temporal evolution of symptoms in some e. Using this unit grid, we were able to allocate most symptoms considered as characteristic for the spectrum displayed by autopsy-confirmed PSP patients.

These 12 clinical features help to diagnose PSP with differing sensitivity and specificity 38 :. We also propose a list of supportive clinical clues to increase diagnostic confidence. Whereas these signs may indeed be helpful to raise suspicion about PSP, we found no clear evidence suggesting that they would indeed contribute reliable information to substantiate the diagnosis of PSP.

Therefore, most of these cases were not identified early or at all for the purposes of routine clinical care, standardized acquisition of natural history data, or inclusion in therapeutic trials. This decision reflects the very rare occurrence of PSP-PLS and PSP-C and the sparse published clinicopathological evidence, which was not perceived to delineate features specific enough to allow ante mortem diagnosis.

The study group declined to risk including patients with predominant PLS or cerebellar ataxia, because this would have weakened the distinction of PSP from motor neuron disease and MSA-C and other adult-onset sporadic cerebellar ataxias, respectively. The MDS-PSP clinical diagnostic criteria are stratified by diagnostic certainty and may therefore be used for different purposes. The concept underlying this stratification has been described in detail elsewhere.

This category is therefore suitable for descriptive epidemiologic studies and clinical care, where it is important not to exclude any cases of true PSP. With the addition of biomarkers to increase diagnostic specificity, these individuals might also be reasonably included in a therapeutic study.

This diagnostic category has been newly introduced in the MDS-PSP criteria in analogy to other progressive neurological diseases, in which defined conditions have been identified with predictable risk of converting to the established disease of interest e. Results: Defined clinical, imaging, laboratory, and genetic findings serve as mandatory basic features, mandatory exclusion criteria, or context-dependent exclusion criteria.

We identified four functional domains ocular motor dysfunction, postural instability, akinesia, and cognitive dysfunction as clinical predictors of PSP.

Within each of these domains, we propose three clinical features that contribute different levels of diagnostic certainty. Explore Mayo Clinic studies testing new treatments, interventions and tests as a means to prevent, detect, treat or manage this condition. Living with any chronic illness can be difficult, and it's normal to feel angry, depressed or discouraged at times.

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The pattern of signs and symptoms can be quite different from person to person. The most frequent first symptom of PSP is a loss of balance while walking. Individuals may have abrupt and unexplained falls without loss of consciousness, a stiff and awkward gait, or slow movement.

As the disease progresses, most people will begin to develop a blurring of vision and problems controlling eye movement. These symptoms may include:. The onset of both diseases is in late middle age. Although individuals with Parkinson's disease markedly benefit from the drug levodopa, people with PSP respond minimally and only briefly to this drug.

The exact cause of PSP is unknown, but research suggests that it involves a gradual deterioration of brain cells in a few specific areas in the brain, mainly in brain stem. The death of brain cells in one of these areas, the substantia nigra, accounts in part for the motor symptoms that PSP and Parkinson's have in common. The hallmark of PSP is the accumulation of abnormal deposits of the protein tau in nerve cells in the brain.

These deposits cause the cells to malfunction and die, which stops the flow of information to other nerve cells. PSP is usually sporadic, meaning that it occurs infrequently and without a known cause. In very few cases, the disease results from mutations in the MAPT gene. This mutation provides faulty instructions for making tau to the nerve cell.