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Progressive Supranuclear Palsy-a Mirror Image of Parkinson’s Disease, A Literature Review of Rehabilitation Strategies
Abstract
Progressive supranuclear palsy (PSP) is a rare neurodegenerative disease which mimic similar to Parkinsonism. PSP advances much quicker than in PD yet no effective medication or therapy to manage PSP available. This literature review aimed to discover the recent advances in the physical therapy treatment options for PSP. Databases such as PubMed, Elsevier and SAGE journal searched for both published and unpublished studies. Last 10-year studies were included in this review. Limited clinical trial conducted in this population due to which a structured protocol or rehabilitation strategies is missing for this condition. Balance exercise and gait training showed potential benefit and music-cued walking demonstrated participant’s satisfaction.
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Treating patients with progressive supranuclear palsy (PSP) is both effective and rewarding. This review aims to share our experience in the proactive management of PSP, considering the patient, the family and the medical context in which the illness unfolds. There are many opportunities to assist your patients, ameliorate their symptoms, reduce their risks and harm, and guide them through the complex medical, social and legal minefield that characterises life with chronic neurological illness. We summarise the challenges of early diagnosis, consider PSP mimics and the role of investigations in excluding these, and discuss the available pharmacological and non-pharmacological treatment strategies to tackle the common and challenging symptoms of PSP. The best treatment will be patient centred and as part of a multidisciplinary team.
Objective
To conduct a systematic review to evaluate exercise and structured physical activity for people living with Progressive Supranuclear Palsy.
Data sources
AMED, CINAHL, Cochrane, EMBASE, Informit, MEDLINE, PEDro, PsycINFO, PubMed and SportDiscus were searched until 18 August 2019. Reference lists of included studies were hand-searched.
Methods
Cochrane guidelines informed review methods. English language peer-reviewed studies of any design, in any setting, were included. Method quality was appraised with the Physiotherapy Evidence Database scale and Joanna Briggs Institute instruments. Data were extracted for study design, sample characteristics and therapy content. Effectiveness was calculated where possible.
Results
Eleven studies were included. Method appraisal showed moderate to high risk of bias. Research designs included three randomized controlled trials, two quasi-experimental studies, one cohort study, four case studies and one case series. Sample sizes ranged from 1 to 24. Exercise interventions included supported and robot-assisted gait training, gaze training, balance re-education and auditory-cued motor training. Dosage ranged from two to five sessions per week over four to eight weeks. End-of-intervention effect sizes were small (6-minute walk test: –0.07; 95% confidence interval (CI): –0.87, 0.73) to moderate (balance: –0.61; 95% CI: –1.40, 0.23; Timed Up and Go: 0.42; 95% CI: –0.49, 1.33) and statistically non-significant. Function, quality of life and adverse events were inconsistently reported.
Conclusions
For people with Progressive Supranuclear Palsy, robust evidence was not found for therapeutic exercises. Reported improvements in walking were derived from two clinical trials. The effects of structured physical activity for people with advanced Progressive Supranuclear Palsy are not known.
Disturbances of balance, gait and posture are a hallmark of parkinsonian syndromes. Recognition of these axial features can provide important and often early clues to the nature of the underlying disorder, and, therefore, help to disentangle Parkinson’s disease from vascular parkinsonism and various forms of atypical parkinsonism, including multiple system atrophy, progressive supranuclear palsy, and corticobasal syndrome. Careful assessment of axial features is also essential for initiating appropriate treatment strategies and for documenting the outcome of such interventions. In this article, we provide an overview of balance, gait and postural impairment in parkinsonian disorders, focusing on differential diagnostic aspects.
Objectives: To understand the benefits and feasibility of using supervised, home-based, music-cued training to improve gait speed and stability in community-dwelling people with Progressive Supranuclear Palsy. Design: Feasibility trial incorporating a single group repeated-measures design. Setting: Human movement laboratory and participants' homes. Interventions: Two training sessions per week, conducted by experienced physiotherapists over 4 weeks. Each home training session consisted of a range of activities in standing or walking, with, and without auditory cues. Rhythmic auditory cues were played via a portable digital music player and consisted of metronome beats and individually chosen, commercially available rhythmic music tracks. Main Outcome Measures: Spatiotemporal gait measures were recorded using an 8 m long GAITRite® mat. Participants walked without cues at self-selected comfortable pace. The Progressive Supranuclear Palsy and Unified Parkinson's Disease Rating Scales were administered at baseline. Addenbrooke's Cognitive Examination-III, Geriatric Depression Scale, Assessment of Personal Music Preference Scale, and Physiological Profile Assessment were administered at baseline and retest. Results: At baseline, two of the five community-dwelling participants with Progressive Supranuclear Palsy walked with normal speed and low gait variability. Of the remainder who walked with slower, more variable patterns, two walked faster at retest, one by a clinically meaningful amount. Four participants reduced their timing variability at retest and three reduced step length variability. All participants reported high satisfaction levels with the program. Conclusions: When delivered at home with the support of caregivers, music-cued gait training can provide a feasible approach to improving disorders of gait stability in people with this rare, degenerative condition. Movement to music is engaging and enjoyable which can facilitate adherence to therapy.
Background:
PSP is a neuropathologically defined disease entity. Clinical diagnostic criteria, published in 1996 by the National Institute of Neurological Disorders and Stroke/Society for PSP, have excellent specificity, but their sensitivity is limited for variant PSP syndromes with presentations other than Richardson's syndrome.
Objective:
We aimed to provide an evidence- and consensus-based revision of the clinical diagnostic criteria for PSP.
Methods:
We searched the PubMed, Cochrane, Medline, and PSYCInfo databases for articles published in English since 1996, using postmortem diagnosis or highly specific clinical criteria as the diagnostic standard. Second, we generated retrospective standardized clinical data from patients with autopsy-confirmed PSP and control diseases. On this basis, diagnostic criteria were drafted, optimized in two modified Delphi evaluations, submitted to structured discussions with consensus procedures during a 2-day meeting, and refined in three further Delphi rounds.
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. Specific combinations of these features define the diagnostic criteria, stratified by three degrees of diagnostic certainty (probable PSP, possible PSP, and suggestive of PSP). Clinical clues and imaging findings represent supportive features.
Conclusions:
Here, we present new criteria aimed to optimize early, sensitive, and specific clinical diagnosis of PSP on the basis of currently available evidence. © 2017 International Parkinson and Movement Disorder Society.
Background:
to date, there are no medical or surgical treatments for progressive supranuclear palsy (PSP). It is possible to speculate that patients with PSP could benefit from rehabilitative treatments designed for Parkinson's disease, including the use of robot-assisted walking training.
Objective:
to evaluate whether the use of the robotic device Lokomat® is superior in PSP patients to the use of treadmill with visual cues and auditory feedbacks (treadmill-plus) in the context of an aerobic, multidisciplinary, intensive, motor-cognitive and goal-based rehabilitation treatment (MIRT) conceived for Parkinsonian patients.
Methods:
we enrolled twenty-four PSP patients. Twelve subjects underwent a 4-week MIRT exploiting the use of the treadmill-plus (MIRT group). Twelve subjects underwent the same treatment, but replacing the treadmill-plus with Lokomat® (MIRT-Lokomat group). Subjects were evaluated with clinical and functional scales at admission and discharge. The primary outcomes were the total PSP Rating Scale (PSPRS) score and its "limb" and "gait" sub-scores. Secondary outcomes were Berg Balance Scale (BBS), Six Minutes Walking test (6MWT) and the number of falls.
Results:
total PSPRS, PSPRS-gait sub-score, BBS, 6MWT and number of falls improved significantly in both groups (p ≤ 0.003 all, except 6MWT, p = 0.032 and p = 0.018 in MIRT-Lokomat and MIRT group respectively). The PSPRS-limb sub-score improved significantly only in the MIRT group (p = 0.002). A significant difference between groups was observed only for total PSPRS, indicating a slightly better improvement for patients in the MIRT group (p = 0.047). No differences between groups were revealed for the other outcomes, indicating that the effect of rehabilitation was similar in both groups.
Conclusions:
Lokomat® training, in comparison with treadmill-plus training, does not provide further benefits in PSP patients undergoing MIRT. Our findings suggest the usefulness of an aerobic, multidisciplinary, intensive, motor-cognitive and goal-based approach for the rehabilitation of patients suffering from such a complex disease as PSP.
Trial registration:
This trial was registered on ClinicalTrials.gov, NCT02109393.
This update discusses novel aspects on genetics, diagnosis, and treatments of atypical parkinsonism published over the past 2 years.
A genome-wide association study identified new genetic risk factors for progressive supranuclear palsy and new genetic conditions presenting with atypical parkinsonism have been described. The clinical criteria for diagnosis of corticobasal degeneration have been revised, and for progressive supranuclear palsy are under revision. Novel molecular techniques to identify possible biomarkers, as in other neurodegenerative disorders, have started being studied on atypical parkinsonian conditions, and although preliminary results seem promising, further studies are urgently warranted. Therapeutic trials based on disease-specific targets have shown no clinical improvement.
The knowledge obtained recently on atypical parkinsonian conditions points out the major deficits in this field. With the expanding phenotypical spectrum of atypical parkinsonian conditions, the early identification of patients has become difficult. The inability of conventional methods to identify these disorders earlier and better than clinicians, and the recent failure of promising therapeutic compounds, highlight the fact that the lack of biomarkers is probably the greatest limitation for developing treatments for these disorders. Thus, current and future research in this direction will be crucial.
Progressive supranuclear palsy is a neurodegenerative disease which affects the brainstem and basal ganglia. Patients present with disturbance of balance, a disorder of downward gaze and L-DOPA-unresponsive parkinsonism and usually develop progressive dysphagia and dysarthria leading to death from the complications of immobility and aspiration. Treatment remains largely supportive but, potentially, treatments based on cholinergic therapy may be useful. As in Alzheimer's disease, the neuronal degeneration is associated with the deposition of hyperphosphorylated tau protein as neurofibrillary tangles but there are important distinctions between the two diseases. Evidence from familial fronto-temporal dementia with parkinsonism linked to chromosome 17 suggests that tau protein deposition is a primary pathogenic event in some neurodegenerative diseases. The understanding of the mechanism of tau deposition in progressive supranuclear palsy is likely to be of importance in unravelling its aetiology.
The clinical diagnosis of progressive supranuclear palsy (PSP) relies on the identification of characteristic signs and symptoms. A proportion of pathologically diagnosed cases do not develop these classic features, prove difficult to diagnose during life and are considered as atypical PSP. The aim of this study was to examine the apparent clinical dichotomy between typical and atypical PSP, and to compare the biochemical and genetic characteristics of these groups. In 103 consecutive cases of pathologically confirmed PSP, we have identified two clinical phenotypes by factor analysis which we have named Richardson's syndrome (RS) and PSP-parkinsonism (PSP-P). Cases of RS syndrome made up 54% of all cases, and were characterized by the early onset of postural instability and falls, supranuclear vertical gaze palsy and cognitive dysfunction. A second group of 33 (32%) were characterized by asymmetric onset, tremor, a moderate initial therapeutic response to levodopa and were frequently confused with Parkinson's disease (PSP-P). Fourteen cases (14%) could not be separated according to these criteria. In RS, two-thirds of cases were men, whereas the sex distribution in PSP-P was even. Disease duration in RS was significantly shorter (5.9 versus 9.1 years, P < 0.001) and age at death earlier (72.1 versus 75.5 years, P = 0.01) than in PSP-P. The isoform composition of insoluble tangle-tau isolated from the basal pons also differed significantly. In RS, the mean four-repeat:three-repeat tau ratio was 2.84 and in PSP-P it was 1.63 (P < 0.003). The effect of the H1,H1 PSP susceptibility genotype appeared stronger in RS than in PSP-P (odds ratio 13.2 versus 4.5). The difference in genotype frequencies between the clinical subgroups was not significant. There were no differences in apolipoprotein E genotypes. The classic clinical description of PSP, which includes supranuclear gaze palsy, early falls and dementia, does not adequately describe one-third of cases in this series of pathologically confirmed cases. We propose that PSP-P represents a second discrete clinical phenotype that needs to be clinically distinguished from classical PSP (RS). The different tau isoform deposition in the basal pons suggests that this may ultimately prove to be a discrete nosological entity.
Clinical syndromes associated with progressive supranuclear palsy-tau pathology now include progressive supranuclear palsy-parkinsonism (PSP-P), in addition to classic Richardson's syndrome (RS) and pure akinesia with gait freezing (PAGF). Although pathological heterogeneity of progressive supranuclear palsy (PSP) has also been established, attempts to correlate this with clinical findings have only rarely provided conclusive results. The aim of this study was to investigate whether regional variations in the types of tau lesions or differences in overall tau load may explain the clinical differences between the RS, PSP-P and PAGF. Quantitative tau pathology assessment was performed in 17 brain regions in 42 cases of pathologically diagnosed PSP (22 RS, 14 PSP-P and 6 PAGF). Neurofibrillary tangles, tufted astrocytes, coiled bodies and thread pathology were quantitated and a grading system was developed separately for each region. Using these grades the overall tau load was calculated in each case. To establish a simplified system for grading the severity of tau pathology, all data were explored to identify the minimum number of regions that satisfactorily summarized the overall tau severity. The subthalamic nucleus, substantia nigra and globus pallidus were consistently the regions most severely affected by tau pathology. The mean severity in all regions of the RS group was higher than in PSP-P and PAGF, and the overall tau load was significantly higher in RS than in PSP-P (P = 0.002). Using only the grade of coiled body + thread lesions in the substantia nigra, caudate and dentate nucleus, a reliable and repeatable 12-tiered grading system was established (PSP-tau score: 0, mild tau pathology, restricted distribution; >7, severe, widespread tau pathology). PSP-tau score was negatively correlated with disease duration (Spearman's rho -0.36, P = 0.028) and time from disease onset to first fall (Spearman's rho -0.49, P = 0.003). The PSP-tau score in PSP-P (median 3, range 0-5) was significantly lower than in RS (median 5, range 2-10, Mann-Whitney U, P < 0.001). The two cases carrying the tau-H2 protective allele had the two lowest PSP-tau scores. We have identified significant pathological differences between the major clinical syndromes associated with PSP-tau pathology and the restricted, mild tau pathology in PSP-P supports its clinical distinction from RS. The grading system we have developed provides an easy-to-use and sensitive tool for the morphological assessment of PSP-tau pathology and allows for consideration of the clinical diversity that is known to occur in PSP.
Study design:
A retrospective case series.
Objective:
To clarify the mid-term results of extensive spinal fusion surgery in patients with Parkinson's disease (PD) or atypical Parkinsonism, especially with respect to their activities of daily living (ADL) over time SUMMARY OF BACKGROUND DATA.: Postural disorders associated with PD lead to spinal imbalance and deformity, resulting in significant disabilities. Clinical outcomes of extensive fusion surgeries in patients with PD over a medium-term follow-up period are currently unknown.
Methods:
Patients with PD who underwent extensive fusion surgery >5 years prior were included. The patients' backgrounds, surgical and radiographic parameters, peri-operative and mechanical complications, and indoor ADL over time were assessed. To assess the activities of severely disabled patients, indoor ADL was classified into four stages: independent; or cane, walker, and wheelchair use.
Results:
Twenty-two patients (mean age, 70.6 years) were included. The mean blood loss, duration of surgery, and fusion levels were 2039 mL, 424 minutes, and 11.9 levels, respectively. Sagittal vertical axis improved from 220 mm preoperatively to 95 mm postoperatively. Peri-operative complications were observed in 17 cases (77%). Before surgery, 1, 5, 12, and 4 cases were independent in ADL, T-cane, walker, and wheelchair use, respectively, which improved to 7, 4, 6, and 4, respectively in one year. Revision surgeries were performed in 8 patients (36%) within 3 years of surgery. In the 3-5 years after the surgery, the ADL of 9 patients worsened due to deterioration of PD. Fifteen cases were followed up over 5 years, at which 1, 2, 4, and 7 cases were independent in ADL, cane, walker, and wheelchair use, respectively.
Conclusions:
Surgical intervention in PD patients with spinal deformities leads to good short-term outcomes; however, the patients' conditions deteriorated because of complications within 3 years and worsening of PD over 3 years after the surgery.
Level of evidence:
4.
Objective:
To explore whether transcranial direct current stimulation (tDCS) over the dorsolateral prefrontal cortex (DLPFC) can improve language capacities in patients with progressive supranuclear palsy (PSP).
Methods:
We used a sham-controlled double-blind crossover design to assess the efficiency of tDCS over the DLPFC in a cohort of 12 patients with PSP. In 3 separate sessions, we evaluated the ability to boost the left DLPFC via left-anodal (excitatory) and right-cathodal (inhibitory) tDCS, while comparing them to sham tDCS. Tasks assessing lexical access (letter fluency task) and semantic access (category judgment task) were applied immediately before and after the tDCS sessions to provide a marker of potential language modulation.
Results:
The comparison with healthy controls showed that patients with PSP were impaired on both tasks at baseline. Contrasting poststimulation vs prestimulation performance across tDCS conditions revealed language improvement in the category judgment task following right-cathodal tDCS, and in the letter fluency task following left-anodal tDCS. A computational finite element model of current distribution corroborated the intended effect of left-anodal and right-cathodal tDCS on the targeted DLPFC.
Conclusions:
Our results demonstrate tDCS-driven language improvement in PSP. They provide proof-of-concept for the use of tDCS in PSP and set the stage for future multiday stimulation regimens, which might lead to longer-lasting therapeutic effects promoted by neuroplasticity.
Classification of evidence:
This study provides Class III evidence that for patients with PSP, tDCS over the DLPFC improves performance in some language tasks.
Objective
To undertake a systematic review and meta-analysis of studies that investigated prognostic factors and survival in patients with progressive supranuclear palsy (PSP) and multiple system atrophy (MSA).
Methods
Publications of at least 10 patients with a likely or confirmed diagnosis of PSP or MSA were eligible for inclusion. Methodological quality was rated using a modified version of the Quality in Prognostic Studies tool. For frequently examined prognostic factors, HRs derived by univariate and multivariate analysis were pooled in separate subgroups; other results were synthesised narratively and HRs could not be reported here.
Results
Thirty-seven studies presenting findings on 6193 patients (1911 PSP, 4282 MSA) fulfilled the inclusion criteria. We identified the following variables as unfavourable predictors of survival. In PSP, PSP-Richardson’s phenotype (univariate HR 2.53; 95% CI 1.69 to 3.78), early dysphagia and early cognitive symptoms. In MSA, severe dysautonomia and early development of combined autonomic and motor features but not MSA phenotype (multivariate HR 1.22; 95% CI 0.83 to 1.80). In PSP and MSA, survival was predicted by early falls (multivariate HR 2.32; 95% CI 1.94 to 2.77), the Neuroprotection and Natural History in Parkinson Plus Syndromes Parkinson Plus Score and the Clinical Global Impression Disease Severity Score but not sex (multivariate HR 0.93; 95% CI 0.67 to 1.28). There was conflicting evidence regarding the prognostic effect of age at onset and stridor.
Conclusion
Several clinical variables were strongly associated with shorter survival in PSP and MSA. Results on most prognostic factors were consistent across methodologically diverse studies; however, the lack of commonality of prognostic factors investigated is a significant limitation.
Background:
Progressive supranuclear palsy (PSP) is an adult onset neurodegenerative condition associated with mobility, balance, speech, swallowing, vision and cognitive changes. The condition is diagnosed using the National Institute for Neurological Disorders and Stroke (NINDS) and the Society of Progressive Supranuclear Palsy (SPSP) criteria. Therapeutic interventions for PSP are important, and a healthcare team should include a physiotherapist, occupational therapist and speech therapist. Mobility, speech and swallowing problems are commonly experienced, and aspiration pneumonia is the leading cause of death. A preliminary search of the literature has indicated that beyond small case series, there is very little evidence to guide specific allied health therapies in PSP. Many strategies for optimizing independence and function for PSP predominately rely on data extrapolated from the study of Parkinson's disease.
Objectives:
The objective of this review was to examine the effectiveness of physical, occupational and speech therapy interventions in the symptomatic management of PSP.
Inclusion criteria types of participants:
This review included participants with PSP as per the NINDS and the SPSP criteria, aged over 40 years of age from all community and clinical settings.
Types of interventions:
This review included studies evaluating any allied health therapy that addressed mobility, vision, swallowing, communication or cognitive/neuropsychiatric difficulties experienced by patients with PSP. Studies examining interventions within the current scope of practice, and emerging interventions (non-invasive brain stimulation therapy) were eligible for inclusion.
Types of comparator:
The effectiveness of interventions of interest was compared with usual care and/or baseline measurements.
Outcomes:
Outcomes of interest included the degree of change, or no change, in the symptoms experienced by patients with PSP relevant to allied health. These included difficulties with mobility, vision, swallowing, communication and cognition.
Types of studies:
All types of quantitative study designs published in English from the time of development of the NINDS and the SPSP criteria in 1996-2014 were considered for inclusion.
Search strategy:
A broad range of synonyms for PSP and a three-step search strategy was utilized to identify possible published and unpublished studies from 11 different databases. An initial limited search via MEDLINE (PubMed), CINAHL, Health Informit, PsycINFO, PEDRO, OTSeeker and SpeechBite was undertaken followed by analysis of the text words contained in the title and abstract, and of the index terms used to describe the article. A second search using all identified keywords and index terms was then undertaken across all included databases. Third, hand-searching was conducted and the reference list of all identified reports and articles was searched for additional studies.
Methodological quality:
Critical appraisal was conducted by two independent reviewers using standardized instruments.
Data extraction:
Quantitative data were extracted from articles included in the review using standardized data extraction tools.
Data synthesis:
As the quantitative articles examined different interventions, pooling of data was not appropriate. Instead, the findings were presented in narrative summary and tabular form.
Results:
Following methodological appraisal, six studies were included in the review. Aside from one small quasi-randomized control study, most studies were small case series and one was a case report. Five of the six studies examined the effectiveness of a range of different physiotherapy rehabilitation programs targeting gait, balance and physical capability, with one study also targeting gaze control. The sixth study examined non-invasive brain stimulation in improving gait and midline symptoms in PSP. No studies examined the effectiveness of occupational therapy or speech therapy interventions in PSP.
Conclusions:
Research into the effectiveness of allied health therapeutic interventions for PSP symptoms is in its infancy. This review found preliminary evidence to support the use of various physiotherapy rehabilitation programs to improve balance, gait and gaze control in people affected by PSP. Further research is urgently required to identify effective interventions to manage mobility, vision, swallowing, communication and cognitive/neuropsychiatric symptoms associated with this devastating condition.
Background
Attentional and executive dysfunctions are associated with falls in community-dwelling elderly individuals and patients with PD. Frontal cognitive dysfunction and falls are frequent symptoms of PSP. We studied to identify the cognitive domains associated with recurrent falls in patients with PSP.
Methods
We performed a battery of neuropsychological tests in 59 individuals with probable PSP. We categorized patients into infrequent fall (≤one fall during the last 12 months, n = 29) or recurrent fall (≥two falls during the last 12 months, n = 30) groups.
Results
UPDRS subscores for axial deficits were significantly higher in the recurrent fall group than the infrequent fall group, but there were no significant differences in UPDRS total motor scores or subscores for bradykinesia, rigidity, and tremor. There was no difference between groups in MMSE scores. ANCOVA with adjustment for confounding factors showed that, recurrent falls were associated with abnormalities in alternating hand movement, alternating square and triangle, RCFT copying task, and ideomotor apraxia. Group difference of abnormalities in Stroop test was marginal (p = 0.054). However, there were no group differences in the frequency of abnormalities in forward or backward digit span, motor impersistence, fist-edge-palm, contrast programming, go-no-go, Luria loop drawing, or Controlled Oral Word Association Tests. Recurrent falls were not associated with memory or language dysfunction.
Conclusions
Recurrent falls in patients with PSP were associated mainly with executive and visuospatial dysfunctions, including 1) impaired coordinated alternating uni- and bimanual motor programming and execution, 2) deficit of attention and decision making in the presence of interference, 3) visuospatial misperception and 4) ideomotor apraxia.
Investigations into prognostic factors in progressive supranuclear palsy have shown conflicting results. We performed a retrospective study in order to identify clinical predictors of survival in clinically diagnosed progressive supranuclear palsy patients referred to our centre.
Data on medical history, survival and five clinical disability milestones (inability to walk unassisted, unintelligible speech, severe dysphagia, dementia and institutionalization) were collected from outpatients' medical records and by a telephone interview to caregivers. Patients were subdivided into Richardson's syndrome and PSP-Parkinsonism according to symptoms during the first 2 years of disease. Survival was analyzed by the Kaplan-Meier method and Cox regression analysis.
Forty-three consecutive patients were enrolled (86% Richardson's syndrome). Motor disturbances were the most frequent symptoms of onset. During the follow-up, 60.5% of patients died after a median survival of 7.1 years (2.2-18). Older age at onset (>63) (HR 2.8; 95% CI: 1.3-5.7; p = 0.007), early dysphagia (HR 2.3; 95% CI: 1-5.3; p = 0.05) and early cognitive deficits (HR 3.6; 95% CI: 1.6-8.2; p = 0.002) were predictors of shorter survival. Compared to PSP-Parkinsonism patients, Richardson's syndrome patients had shorter survival and higher mortality risk although not statistically significant (HR 3 95% CI: 0.9-9.9; p = 0.07). Seventy-seven percent of patients developed severe disability during follow-up: shorter time to the first clinical disability milestone predicted shorter survival (HR 7.8; 95% CI: 2.3-26; p = 0.0008). Conclusions: early dysphagia, cognitive impairment, older age at onset, and time to disability were predictors of shorter survival; Richardson's syndrome had a less favorable course than PSP-Parkinsonism. Clinical milestones should be considered as possible endpoints in future clinical trials.
Background:
Patients with idiopathic Parkinson's disease (PD) or atypical Parkinsonism (AP) often present with orthostatic hypotension (OH) as a result of the dysautonomia associated with the disease or as a side effect of the dopaminergic medications used to treat it. Our recent study suggested that OH negatively impacts gross motor, balance, and cognitive functions in patients with PD.
Objective:
To determine if correcting the orthostatic hypotension (OH) of patients with PD or AP improves their gross motor, balance, and cognitive functions.
Methods:
Forty patients with PD or AP were assessed before and after correcting their OH using a staged approach with a goal of SBP >80 when standing and SBP <180 when laying. Step 1 of treatment included reducing antihypertensive medications, as possible, maintaining hydration with 1500cc/day, decreasing dietary salt, wearing high compression stockings, and keeping the head of bed elevated at 30 degrees when supine. If SBP <80 with standing after step 1, then treatment was started with fludrocortisone and/or midodrine.
Results:
Patients' OH was managed as part of a rehabilitation program. Tests such as the Motor and Cognitive Functional Independence Measures, Berg Balance Scale, Two Minute Walking test, and the Finger Tapping test showed significant improvements (p < 0.05) in their gross motor, walking, balance and cognitive function with our OH management plan. No significant differences between admission and discharge were found in the Timed Up and Go test.
Conclusion:
Our data suggest that monitoring and correcting the OH of patients with PD or AP improves their gross motor, balance, and cognitive function.
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.
Progressive supranuclear palsy (PSP) was first recognized as a distinct morbid entity by Richardson, Steele and Olszewski a quarter century ago. Subsequent experience has confirmed and extended their original observations. PSP has become familiar as a chronic progressive disorder with extrapyramidal rigidity, bradykinesia, gait impairment, bulbar palsy, dementia and a characteristic supranuclear ophthalmoplegia. It is an important cause of parkinsonism. Its etiology remains obscure. Familial concentrations have not been observed. Some cases exhibit no oculomotor dysfunction. Dementia is usually mild. Recent neuropsychological studies have defined features consistent with frontal lobe cortical dysfunction. Seizures and paroxysmal EEG activity may occur. CT and MRI scans show midbrain atrophy early and later atrophy of the pontine and midbrain tegmentum and the frontal and temporal lobes. PET scans have shown frontal hypometabolism and loss of striatal D-2 dopamine receptors. Postmortem studies have documented involvement of both dopaminergic and cholinergic systems. Treatment remains palliative and unsatisfactory.
The clinical diagnosis of PSP depends primarily on the history and the physical findings. Clinicians should be alerted to the possibility of this condition in assessing patients presenting with atypical parkinsonism and other complex extrapyramidal syndromes in late middle age or later. The differential diagnosis includes MSA (both OPCA and SND), PD, CBD and cerebrovascular disease. PD is probably the most common erroneous diagnosis. Unfortunately, pathognomonic signs do not usually appear until several years, after symptom onset. No specific laboratory test is yet available. Neuroimaging studies show characteristic anatomic alterations only late in the course of the illness and must be correlated with the clinical findings.
Progressive supranuclear palsy (PSP) is characterized clinically by supranuclear gaze palsy, neck dystonia, parkinsonism, pseudobulbar palsy, gait imbalance with frequent falls and frontal lobe-type dementia. In the advanced typical case, when supranuclear gaze palsy and other main features are present diagnosis is relatively easy. Diagnostic problems, though, are frequent in the early stages due to the variable clinical presentation and in those atypical cases in which gaze palsy does not develop or that present as a severe dementia disorder or as an isolated akinetic-rigid syndrome. In this review we summarize the clinical features of PSP and emphasize those aspects helpful in the differential diagnosis with Parkinson's disease and other motor and cognitive disorders that can pose difficult diagnostic problems. Clinical diagnostic criteria are also discussed and modifications of those currently in used are proposed.
We present the preliminary neuropathologic criteria for progressive supranuclear palsy (PSP) as proposed at a workshop held at the National Institutes of Health, Bethesda, MD, April 24 and 25, 1993. The criteria distinguish typical, atypical, and combined PSP. A semiquantitative distribution of neurofibrillary tangles is the basis for the diagnosis of PSP. A high density of neurofibrillary tangles and neuropil threads in the basal ganglia and brain-stem is crucial for the diagnosis of typical PSP. Tau-positive astrocytes or their processes in areas of involvement help to confirm the diagnosis. Atypical cases of PSP are variants in which the severity or distribution of abnormalities deviates from the typical pattern. Criteria excluding the diagnosis of typical and atypical PSP are large or numerous infarcts, marked diffuse or focal atrophy, Lewy bodies, changes diagnostic of Alzheimer's disease, oligodendroglial argyrophilic inclusions, Pick bodies, diffuse spongiosis, and prion protein-positive amyloid plaques. The diagnosis of combined PSP is proposed when other neurologic disorders exist concomitantly with PSP.
We investigated the validity and reliability of diagnoses made by eight neuropathologists who used the preliminary NINDS neuropathologic diagnostic criteria for progressive supranuclear palsy (PSP) and related disorders. The specific disorders were typical, atypical, and combined PSP, postencephalitic parkinsonism, corticobasal ganglionic degeneration, and Pick's disease. These disorders were chosen because of the difficulties in their neuropathologic differentiation. We assessed validity by measuring sensitivity and positive predictive value. Reliability was evaluated by measuring pairwise and group agreement. From a total of 62 histologic cases, each neuropathologist independently classified 16 to 19 cases for the pairwise analysis and 5 to 6 cases for the group analysis. The neuropathologists were unaware of the study design, unfamiliar with the assigned cases, and initially had no clinical information about the cases. Our results showed that with routine sampling and staining methods, neuropathologic examination alone was not fully adequate for differentiating the disorders. The main difficulties were discriminating the subtypes of PSP and separating postencephalitic parkinsonism from PSP. Corticobasal ganglionic degeneration and Pick's disease were less difficult to distinguish from PSP. The addition of minimal clinical information contributed to the accuracy of the diagnosis. On the basis of results obtained, we propose clinicopathologic diagnostic criteria to improve on the NINDS criteria.
The morphology of a neuron is determined by its cytoskeletal scaffolding. Thus proteins that associate with the principal cytoskeletal components such as the microtubules have a strong influence on both the morphology and physiology of neurons. Tau is a microtubule-associated protein that stabilizes neuronal microtubules under normal physiological conditions. However, in certain pathological situations, tau protein may undergo modifications, mainly through phosphorylation, that can result in the generation of aberrant aggregates that are toxic to neurons. This process occurs in a number of neurological disorders collectively known as tauopathies, the most commonly recognized of which is Alzheimer's disease. The purpose of this review is to define the role of tau protein under normal physiological conditions and to highlight the role of the protein in different tauopathies.
Progressive supranuclear palsy: a heterogeneous degeneration involving the brainstem, basal ganglia and cerebellum with vertical supranuclear gaze and pseudobulbar palsy, nuchal dystonia and dementia
- J C Steele
- J C Richardson
- J Ilsezewski
Steele JC, Richardson JC, Ilsezewski J.
Progressive
supranuclear
palsy:
a
heterogeneous degeneration involving the
brainstem, basal ganglia and cerebellum
with vertical supranuclear gaze and
pseudobulbar palsy, nuchal dystonia and
dementia. Arch Neurol. 1964;10:333-359.