Early Progressive Supranuclear Palsy Research Articles

Circular walking is useful for assessing the risk of falls in early progressive supranuclear palsy.

Progressive supranuclear palsy (PSP) is characterized by early onset postural instability and frequent falls. Circular walking necessitates dynamic postural control, which is impaired in patients with PSP. We aimed to explore gait parameters associated with the risk of falls in patients with PSP, focusing on circular walking. Sixteen drug-naïve patients with PSP, 22 drug-naïve patients with Parkinson's disease (PD), and 23 healthy controls were enrolled. Stride lengths/velocities and their coefficients of variation (CV) during straight and circular walking (walking around a circle of 1-m diameter) were measured under single-task and cognitive dual-task conditions. Correlation analysis was performed between gait parameters and postural instability and gait difficulty (PIGD) motor subscores, representing the risk of falls. Patients with PSP had significantly higher CVs of stride lengths/velocities during circular walking than those during straight walking, and the extent of exacerbation of CVs in patients with PSP was larger than that in patients with PD under single-task conditions. Stride lengths/velocities and their CVs were significantly correlated with PIGD motor subscores in patients with PSP only during single-task circular walking. In addition, patients with PSP showed progressive decrements of stride lengths/velocities over steps only during single-task circular walking. Worse gait parameters during circular walking are associated with an increased risk of falls in patients with PSP. Circular walking is a challenging task to demand the compromised motor functions of patients with PSP, unmasking impaired postural control and manifesting sequence effect. Assessing circular walking is useful for evaluating the risk of falls in patients with early PSP.

Brain FDG-PET correlates of saccadic disorders in early PSP.

New diagnostic criteria of Progressive Supranuclear Palsy (PSP) have highlighted the interest of Eye Movement Records (EMR) at the early stage of the disease. To investigate the metabolic brain correlates of ocular motor dysfunction using [18F] Fluorodeoxyglucose Positron Emission Tomography (FDG-PET) in early PSP. Retrospective observational descriptive study on longitudinal data with patients who underwent EMR and FDG-PET at the stage of suggestive and possible PSP according to Movement Disorders Society criteria. Longitudinal follow-up enables to confirm diagnosis of probable PSP. Using the Statistical Parametric Mapping software, we performed whole-brain voxel-based correlations between oculomotor variables and FDG-PET metabolism. Thirty-seven patients with early PSP who fulfilled criteria of probable PSP during the follow-up were included. Decrease in the gain of vertical saccades correlated with reduced metabolism in Superior Colliculi (SC). We also found a positive correlation between mean velocity of horizontal saccades and SC metabolism as well as dorsal nuclei in the pons. Finally, increase in horizontal saccades latencies correlated with decrease of posterior parietal metabolism. These findings suggest the early involvement of SC in saccadic dysfunction in the course of PSP.

Postural control in Parkinsonisms during a short static sway

Neurological diseases, such as Parkinsonisms, are often associated with static postural instability. Progressive supranuclear palsy (PSP) is a rare neurodegenerative disease classified among atypical Parkinsonisms. In the earliest stages, PSP is similar to Parkinson’s disease (PD) [1]. Static postural stability is an important contributor to the balance control framework and balance impairment can be quantified with a postural sway measure [2]. The main goal of our study was to compare postural sway changes in both PSP and PD subjects, using a standing single task of 5-6 seconds, in order to prove that a shorter sway time may be useful to distinguish Parkinsonisms. We assessed fifteen individuals with early PSP and fifteen individuals with recent diagnosis of PD (De Novo PD). Stabilometric analysis was performed for the evaluation of balance through a BTS Bioengineering system. The patient was instructed to stand on the force plate with the eyes open and measures of 5-6 seconds were taken. To find differences between the groups, univariate statistical analysis on sway data was conducted, and an alpha significance level was set to p-value < 0.05. The statistical analysis showed significant differences between De Novo PD and PSP groups for Medio- Lateral (M-L) sway (p-value=0.01), M-L range (p-value=0.023) and radius (p-value=0.026); minimum oscillation from the center of gravity and area showed a statistical trend with a p-value slightly above the 0.05 (p-value=0.056 and p-value=0.061, respectively). Several studies have demonstrated that balance dysfunction in PD is directionally dependent [2,3]. In agreement with our data, patients with atypical Parkinsonism show balance impairment on M-L direction as attested by augmented M-L sway, M-L range and radius. These results indicate that a short static sway of 5-6 seconds, could provide the clinician with a reliable and non-invasive tool to distinguish PSP from PD since the earliest stages.

Workshop Compiled

Progressive supranuclear palsy (PSP) is a type of neurodegenerative extrapyramidal syndrome. The prevalence of PSP in studies is found to be 5.8-6.5 per 100,000 individuals with a slightly male preponderence. Onset is usually between 55 and 70 years of age and median survival is around 6 years after the onset of symptomatology.It is characterized by motor symptoms, such as postural instability, rigidity, akinesia, supranuclear gaze palsy, pseudobulbar palsy; levodopa-unresponsive parkinsonism, and behavioral and cognitive symptoms. Early PSP is also difficult to differentiate from PD; as it shares many features like abnormalities in gait, speech, and eye movements. Neuropsychiatric symptoms commonly observed in patients with PSP are dementia, apathy, depression, anxiety, disorders of sleep and disinhibition.A 60 year old man presented with impaired memory, disturbed sleep and restless behaviour for 2months in geriatric mental health outpatient department. He had a history of tremors on both the hands and stiffness of body which was gradually progressive for last 4 years. They consulted a neurologist 1.5 years back as his symptoms were severe enough to hamper in day to day functioning. He was diagnosed as a case of idiopathic Parkinson’s Disease and was prescribed Tab Levodopa 100mg and Carbidopa 25mg combination preparation thrice daily. On medication within 2months, family members reported decrease in his symptoms. For last 6months new symptoms like frequent falls during walking without any precipitant developed. Falls usually occurred within a few steps of walking mostly towards the left side and following which he sustained an injury over his left eye leading to lower lid ectropion. The activity of the patient became restricted and he started to remain confined to his bed for the fear of falls since last 3months. They consulted a physician again and he was prescribed Tab Trihexyphenydyl 2mg three times a day and dose of Tab Levodopa 100mg and Carbidopa 25mg combination increased to four times a day and Tab Levodopa 100mg and Carbidopa 25mg combination contolled relase preparation was added at bedtime. After taking those medications the frequency of falls increased, forgetfulness appeared, sleep got disturbed, at night he becomes restless and some confusion in behavior like pointing things, picking bed linen were noticed during evening hours.On examination the patient had prominent vertical wrinkling of forehead, wide opened eyes with reduced blinking, ‘procerus sign’ was present. His speech revealed hypophonia and reduced fluency. On the first two days his orientation was fluctuating; from the third day no abnormality was noticed in his mental state. Neurological examination revealed wide based festinating gait, intention tremor in upper limb, lead pipe rigidity in all four limbs bilaterally(right>left), axial rigidity and impaired balance and coordination; and supranuclear gaze palsy.During the hospital stay the anticholinergic drug (trihexyphenydyl 2mg) and Tab Levodopa 100mg and Carbidopa 25mg combination contolled relase preparation was withheld; Tab Melatonin 5mg was added along with other drugs were continued. Within 2days of hospitalization, his sleep improved, restlessness and confusion in behavior decreased, also his cognition was improved.Workshop Description:Approach to Parkinson plus syndromes presenting in Geriatric Psychiatric population.Case scenarios from the literature.Discussion on diagnostic and management issues.Methods/Issues:Progressive supranuclear palsy (PSP) is often difficult to discriminate clinically from idiopathic Parkinson’s disease (PD). Diagnosis in early stage is important for maximal benefit from disease modifying treatment for PSP. Delirium is defined as an acute organic brain syndrome which presents with decreased level of consciousness, varied psychomotor activity, wake-sleep rhythm disorders, cognitive impairment and attention deficits. High dose of Levodopa in Parkinson’s disease is reported to cause confusion and psychosis.Moreover dopaminergic drug in Progressive Supranuclear Palsy has response in only 20-40% cases.Anticholinergic drugs in ageing brain with comorbidities are known to cause confusion and delirium.Learning Objectives:Parkinsonism plus syndrome as a heterogeneous degenerative neurological disorders that differs from the classical idiopathic Parkinson’s disease in certain associated clinical features, poor response to levodopa, distinctive pathological characteristics and poor prognosis. Associated clinical features include symmetrical onset, infrequent or atypical tremor, prominent rigidity in axial musculature, bradykinesia, early postural instability, supranuclear gaze palsy, early autonomic failure, pyramidal affection, cerebellar involvement, alien limb phenomenon, apraxia and significant early cognitive dysfunction in some cases. Progressive supranuclear palsy (PSP), multiple system atrophy (MSA) and dementia with Lewy body disease (DLB) are commoner disorders. Less frequent disorders are cortico-basal ganglionic degeneration (CBGD), frontotemporal dementia with chromosome 17 (FTDP-17), Pick’s disease, parkinsonian-dementia complex of Guam, Pallidonigral degeneration, Wilson’s disease and a rigid variant of Huntington’s disease.Conclusions/ Strategies:Patients with Parkinsonism-plus syndromes represent a relatively small portion of Parkinsonism patients.They have wide spectrum of disease phenotypes associated with these disorders and the often subtle clinical differences, establishing the correct diagnosis, especially at disease onset, can be difficult despite serial clinical observations and repeated neurological examination.

Energy expenditure, body composition and dietary habits in progressive supranuclear palsy.

IntroductionLittle is known about metabolic changes in progressive supranuclear palsy. Goals of the present study are to: (1) investigate whether early progressive supranuclear palsy is associated with changes in energy expenditure, body composition and dietary intake compared with Parkinson’s disease and healthy controls; (2) assess the accuracy of the Harris–Benedict equation to predict measured rest energy expenditure in progressive supranuclear palsy; (3) verify differences according to sex, phenotypes, disease severity and presence of dysphagia in progressive supranuclear palsy.MethodsTwenty-one progressive supranuclear palsy, 41 Parkinson’s disease and nine healthy controls were included. Rest energy expenditure was assessed with indirect calorimeter, body composition with bio-impedance analysis and physical activity and dietary intake were estimated with a validated frequency questionnaire. Parametric testing was used to analyze differences between groups.ResultsProgressive supranuclear palsy showed reduced total daily energy expenditure and physical activity compared to both other cohorts (p < 0.001) and a tendency toward lower fat-free mass compared to Parkinson’s disease (p > 0.05). Limited accuracy was shown for the Harris–Benedict equation (accurate prediction frequency < 60%). Greater disease severity was associated with lower rest energy expenditure (p = 0.030), fat-free mass (p = 0.026) and muscle mass (p = 0.029).ConclusionGreater disease severity is associated with reduction in rest energy expenditure likely due to the reduction in lean mass and muscle mass. Such data may pave the way to clinical trials evaluating the efficacy of muscle-targeted nutritional support and physical therapy in preserving muscle mass and improving motor performances in progressive supranuclear palsy at early stages.Supplementary InformationThe online version contains supplementary material available at 10.1007/s00415-021-10846-6.

Gait analysis may distinguish progressive supranuclear palsy and Parkinson disease since the earliest stages

Progressive supranuclear palsy (PSP) is a rare and rapidly progressing atypical parkinsonism. Albeit existing clinical criteria for PSP have good specificity and sensitivity, there is a need for biomarkers able to capture early objective disease-specific abnormalities. This study aimed to identify gait patterns specifically associated with early PSP. The study population comprised 104 consecutively enrolled participants (83 PD and 21 PSP patients). Gait was investigated using a gait analysis system during normal gait and a cognitive dual task. Univariate statistical analysis and binary logistic regression were used to compare all PD patients and all PSP patients, as well as newly diagnosed PD and early PSP patients. Gait pattern was poorer in PSP patients than in PD patients, even from early stages. PSP patients exhibited reduced velocity and increased measures of dynamic instability when compared to PD patients. Application of predictive models to gait data revealed that PD gait pattern was typified by increased cadence and longer cycle length, whereas a longer stance phase characterized PSP patients in both mid and early disease stages. The present study demonstrates that quantitative gait evaluation clearly distinguishes PSP patients from PD patients since the earliest stages of disease. First, this might candidate gait analysis as a reliable biomarker in both clinical and research setting. Furthermore, our results may offer speculative clues for conceiving early disease-specific rehabilitation strategies.

Diagnostic accuracy of MR planimetry in clinically unclassifiable parkinsonism

IntroductionQuantitative MR planimetric measurements were reported to discriminate between progressive supranuclear palsy (PSP) and non-PSP parkinsonism, yet few data exist on the usefulness of these markers in early disease stages. MethodsThe pons-to-midbrain area ratio (P/M) and the Magnetic Resonance Parkinsonism Index (MRPI) as well as new indices, termed P/M2.0 and MRPI2.0, multiplying the former by a ratio of the third ventricle (3rdV) width/frontal horns (FH) width, were calculated on T1-weighted images in 84 patients with clinically unclassifiable neurodegenerative parkinsonism (CUP) at the time of imaging. Areas under the curve (AUCs) of these markers for predicting future PSP was determined. The final clinical diagnosis was made after at least 24 months of follow-up. ResultsFinal diagnosis was Parkinson's disease in 55 patients, multiple system atrophy in 12 cases, and PSP in 17. At baseline imaging, patients with a final PSP diagnosis had significantly higher MRPI, P/M, MRPI2.0 and P/M2.0 values compared to the other groups. AUCs in discriminating between future PSP and non-PSP parkinsonism were 0.91 for both the P/M and the MRPI and 0.98 for the P/M2.0 and the MRPI2.0. ConclusionsBrainstem-derived MR planimetric measures yield high diagnostic accuracy for separating PSP from non-PSP parkinsonism in early disease stages when clinical criteria are not yet fully met. Consistent with the underlying pathology in PSP, our study suggests that inclusion of 3rdV width makes P/M2.0 and MRPI2.0 more accurate in diagnosing early stage PSP patients than the P/M and MRPI.

DOUBLE JEOPARDY: UNTANGLING DEPRESSION, PARKINSON'S DISEASE & FRONTOTEMPORAL DEMENTIA IN CLINICAL PRACTICE WITH BEDSIDE COGNITIVE TESTING

Introduction Progressive supranuclear palsy is a taupathy disorder often mistaken on diagnosis by other neurocognitive disorders such as Parkinson's (PD) and Alzheimer's (AD) disease amongst other. PSP tends to be diagnosed in the later course of the disease and by time of diagnosis, individuals have a median survival of 7?years. PSP is a disease in which a diagnosis and treatment is done in a multidisiplinary approach involving collaboration of Psychiatry and Neurology. As it was seen in this clinical case which describes a patient with undetected progressive supranuclear palsy who were referred to a university hospital psychiatric emergency services facility for treatment of late onset symptoms and signs attributed to primary psychopathology related to behavioral variant of frontotemporal lobar degeneration (FTLDbv). Methods The patient described in the clinical vignette underwent a comprehensive neuropsychiatric assessment, given that the accuracy of the diagnosis of FTLDbv was in doubt. The clinical interview identified no significant prior developmental, medical, neurological, psychiatric, or substance use disorders; no family history of neuropsychiatric disturbance; and no significant psychosocial stressor before the onset of his neuropsychiatric condition at age 59. Bedside cognitive testing showed a Geriatric Depression Scale (GDS) score suggestive of mild symptoms of depression, and would be unlikely to explain his new onset psychosis. His subclinical Executive Interview 25 (EXIT 25) score and normal Mini Mental State Examination (MMSE) were not indicative of a dementia syndrome. Given the strong temporal relationship between the onset of his behavioral changes and perceptual disturbances and the start of levodopa/carbidopa, this medication was discontinued. He was admitted to the inpatient psychiatric service for observation. He was started initially on an atypical antipsychotic, but had this medication discontinued, as he no longer exhibited symptoms of psychosis. His citalopram was titrated to 40mg daily to optimize treatment of his major depressive disorder. Patient was discharge with complete resolution of psychotic symptoms and with diagnosis of Depressive disorder, unspecified and medication-induced psychotic disorder with delusions and hallucinations. A dopamine transporter (DaT) protein scan, a marker for presynaptic terminals in dopaminergic nigrostriatal neuros (marker for PD) and or iodine-123-metaiodobenzylguanadine (MIBG) myocardial scintigraphy (marker for DLB), was not performed. Results CASE REPORT: A 59-year-old, left handed, previously healthy gentleman was brought by police to a university hospital psychiatry emergency services for evaluation of acute safety concerns, regarding behavioral and personality changes. Patient was admitted to the hospital displaying motor symptoms with appearance of jaw tremor, ataxia, and urinary incontinence. After a negative brain MRI and head CT scan, the neurology team concluded that he had Parkinson`s disease and patient was discharged on levodopa/carbidopa (25?mg/?100 mg) QID and citalopram 20?mg daily for associated depressive symptoms with no benefit. After discharge from the hospital, he had become increasingly impulsive, hypersexual and engaging in risky behaviors with firearms. Persistent and progressive change in personality and behavior were the earliest displayed signs and they remained the most prominent features of his condition. All of these disturbances worsened after patient was started on levodopa/carbidopa. After evaluation by the psychiatry consultation and liaison service, a Mental status examination revealed cognitive and neurovegetative symptoms of depression as well as auditory illusions and concerns that a stranger had invaded his home. He denied manic symptoms. No suicidal and homicidal thoughts. Despite extensive neurological and neuropsychological evaluation 10-months later, surprisingly, it was established the diagnosis of progressive supranuclear palsy (PSP), as at that visit the patient presented with predominantly delay axial Parkinsonism, supranuclear gaze palsy, and increased falls due to postural instability. A neuropsychological assessment provided evidence of an executive syndrome of subcortical frontal type. Conclusions Progressive supranuclear palsy is a debilitating taupathy disorder that often is mistaken on diagnosis by other neurocognitive disorders such as Parkinson's dementia, Alzheimer's dementia and Frontotemporal lobar degeneration amongst others. Thus, making PSP diagnosis difficult at initial presentation and often presenting later in life. PSP diagnosis requires a multidisciplinary approach, a collaboration between Psychiatry and Neurology to piece together the complex problems that often manifest in challenging neuropsychiatric syndromes. The possibility of PSP should be considered in the differential diagnosis of late onset psychiatric syndromes. Early PSP diagnosis is imperative for both patients and physicians, as proper treatment will be started without delay to address PSP symptomatology. Thus, reducing the burden of patient and family, as well as reducing unnecessary diagnostic tests, hospitalizations and sub-optimal psychiatric treatment. It is imperative that providers from all specialties be aware of PSP early presentation and how it can be mistaken, specially in early stages, with other neurocognitive disorders in order to make proper referrals for the most effective treatment available. This research was funded by: N/A

Procerus Sign: Mechanism, Clinical Usefulness, and Controversies.

This sign is observed in atypical parkinsonism mainly in Progressive Supranuclear Palsy. The exact mechanism of this sign is not clear but the contraction of the Corrugator Supercilii muscle is the most important factor for the generation of vertical forehead creases. Though the wrinkling of forehead is a complex phenomenon involving multiple muscles but the 'Corrugator sign' would be a better term to describe this phenomenon. Despite the controversies regarding the mechanism and nomenclature, the 'Procerus sign' remains an important clinical clue for early Progressive Supranuclear palsy.

Neuropsychiatric and cognitive profile of early Richardson's syndrome, Progressive Supranuclear Palsy-parkinsonism and Parkinson's disease

IntroductionThe two main variants of Progressive Supranuclear Palsy (PSP), Richardson's syndrome (PSP-RS) and PSP-parkinsonism (PSP-P), share motor and non-motor features with Parkinson's disease (PD) particularly in the early stages. This makes the precocious diagnosis more challenging. We aimed at defining qualitative and quantitative differences of neuropsychiatric and neuropsychological profiles between PSP-P, PSP-RS and PD patients recruited within 24 months after the onset of symptoms, in order to clarify if the identification of peculiar cognitive and psychiatric symptoms is of help for early PSP diagnosis. MethodsPD (n = 155), PSP-P (n = 11) and PSP-RS (n = 14) patients were identified. All patients were submitted to clinical, neurological, neuropsychiatric diagnostic evaluation and to a comprehensive neuropsychiatric and neuropsychological battery. Predictors of PSP-P and PSP-RS diagnosis were identified by multivariate logistic regressions including neuropsychiatric and neuropsychological features that differed significantly among groups. ResultsThe three groups differed significantly at the Apathy Rating Scale score and at several neuropsychological domains. The multivariate logistic regressions indicated that the diagnosis of PSP-RS was predicted by phonological verbal fluency deficit whereas the presence of apathy significantly predicted the PSP-P diagnosis. ConclusionPeculiar neuropsychiatric and neuropsychological symptoms are identifiable very precociously in PSP-P, PSP-RS and PD patients. Early phonological verbal fluency deficit identifies patients with PSP-RS whereas apathy supports the diagnosis of PSP-P.

Neuropathologic features of suicide victims who presented with acute poststroke depression: significance of association with neurodegenerative disorders.

To investigate the neuropathologic characteristics of poststroke depression (PSD) leading to suicide, we retrospectively selected deceased subjects who had been diagnosed as having early PSD. Cases were divided into subjects who had committed suicide and those who had not. Neuropathologic examinations, including immunohistochemistry, were conducted. Twenty-four subjects fulfilled criteria for early PSD; 11 of these had committed suicide, and the other 13 had not. Lesion type, size of stroke, and location of stroke were variable but did not differ significantly between the groups. Alzheimer disease-related pathology stages also did not differ between the groups. Argyrophilic grain disease was found in both the suicide group (6 of 11) and the nonsuicide group (2 of 13); there were 2 highly possible cases of early progressive supranuclear palsy in the suicide group. Together, argyrophilic grain disease and progressive supranuclear palsy were found significantly more frequently in suicide cases than in nonsuicide cases (p = 0.01). These data suggest that overlapping 4-repeat tauopathies, which include argyrophilic grain disease and progressive supranuclear palsy, might be an important aggravating factor of PSD that could lead to suicide. The presence of other neurodegenerative diseases does not preclude PSD because the prevalence of these diseases in older persons suggests that they might often occur concomitantly.

Early Stage of Progressive Supranuclear Palsy: A Neuropathological Study of 324 Consecutive Autopsy Cases.

Diagnosing clinical progressive supranuclear palsy (PSP) is challenging. We hypothesize that there are more cases of pathological PSP than have been clinically identified, but its diagnosis is challenging because the initial lesions and progression of PSP have not yet been clarified. The purpose of our study was to clarify the incidence of PSP in consecutive autopsy cases and identify pathological characteristics of early PSP. We investigated 324 consecutive autopsy patients from a general geriatric hospital (age, mean±SD=82.5±8.7 years). Paraffin sections of the midbrain were immunostained with anti 4-repeat tau antibodies (RD4). We selected cases showing RD4-positive neurofibrillary tangles and tufted astrocytes in the midbrain sections. Then, we used anti-phosphorylated tau antibody to immunostain sections from the basal ganglia, subthalamic nucleus, midbrain, pons, medulla, and cerebellum. Of the 324 patients, 35 had RD4-positive structures in the midbrain. From these 35 cases, we excluded those for which autopsies confirmed definite PSP (n=5) and cases of corticobasal degeneration (n=1), Alzheimer's disease (n=11), dementia of grain (n=10), and neurofibrillary tangles predominant forms of senile dementia (n=2), leaving 8 cases. We diagnosed these 8 cases as pure PSP-type tauopathy. Pure PSP-type tauopathy was detected in 2.5% of the consecutive autopsy cases, and this incidence was 1.6 times greater than that of neuropathologically definite PSP. This pure PSP-type tauopathy likely indicates preclinical stages of PSP. Furthermore, the novel neuropathological finding, which we term "preclinical PSP," is unique and has not previously been reported. In order to elucidate the causes and pathological mechanisms of PSP, preclinical PSP should be investigated further.

Gait and computerized dynamic posturography (CDP) aspects in early progressive supranuclear palsy (PSP) - a case report.

BACKGROUND: Posture and gait instability may cause of morbidity in individuals with progressive supranuclear palsy (PSP). OBJECTIVE: To quantitatively measure balance control by using computerized dynamic posturography (CDP) and to assess gait analysis in early PSP.CASE REPORT: She was evaluated for Berge balance scale, Functional Independence Measure (FIM) and postural stability using CDP device in early PSP with still able to walk or stand unassisted. Also, Gait analysis was conducted using an 8 M-camera Vicon 612 data capturing system set. Berge balance scale improved from 41/56 to 48/56. The score of FIM improved from 71/126 points to 95/126 points in early PSP. In CDP analysis, there was a decrease of composite equilibrium score (38 %). There was an increase of composite equilibrium score (59%) after three months of treatment. In gait analysis, there was no difference of gait parameters after three months of treatment in early PSP.CONCLUSIONS: Both CDP and gait analysis are important quantitative tools in the assessment of posture and gait instability as well as allow for early disclosure of the failure of the postural control system in early PSP.

Gait and Computerized Dynamic Posturography (CDP) Aspects in Early Progressive Supranuclear Palsy (PSP) - A Case Report

BACKGROUND: Posture and gait instability may cause of morbidity in individuals with progressive supranuclear palsy (PSP). OBJECTIVE: To quantitatively measure balance control by using computerized dynamic posturography (CDP) and to assess gait analysis in early PSP.CASE REPORT: She was evaluated for Berge balance scale, Functional Independence Measure (FIM) and postural stability using CDP device in early PSP with still able to walk or stand unassisted. Also, Gait analysis was conducted using an 8 M-camera Vicon 612 data capturing system set. Berge balance scale improved from 41/56 to 48/56. The score of FIM improved from 71/126 points to 95/126 points in early PSP. In CDP analysis, there was a decrease of composite equilibrium score (38 %). There was an increase of composite equilibrium score (59%) after three months of treatment. In gait analysis, there was no difference of gait parameters after three months of treatment in early PSP.CONCLUSIONS: Both CDP and gait analysis are important quantitative tools in the assessment of posture and gait instability as well as allow for early disclosure of the failure of the postural control system in early PSP.

Direction specific preserved limits of stability in early progressive supranuclear palsy: A dynamic posturographic study

ObjectivesTo quantitatively detect the nature of balance impairment in patients with progressive supranuclear palsy (PSP) using dynamic posturography. MethodsTwenty clinically diagnosed PSP patients (8 women, 12 men; age: 62.1±7.7 years; duration: 2.6±1.3 years) and 20 healthy controls were studied. All subjects were right side dominant. They were evaluated by dynamic posturography (Biodex, USA). The measurements included (i) balance indices: ability to control balance in all directions (overall balance index, OBI), front to back (anterior–posterior index, API) and side-to-side (medio-lateral index, MLI), and (ii) the limits of stability (LOS) in 8 directions: forward (FW), backward (BW), right (RT), left (LT), forward-right (FW-RT), forward-left (FW-LT), backward-right (BW-RT) and backward-left (BW-LT). ResultsCompared to controls, patients showed significantly higher OBI (p<0.001), API (p=0.003) and MLI (p<0.001), implying impaired balance. The total LOS score was significantly lower (implying poor stability) in PSP than in controls (18.3±7.3 vs. 28.4±8.5, p<0.001). Patients took significantly longer time to complete LOS test (262.7±33.0s vs. 135.4±20.6s, p<0.001). Direction-wise analysis showed that PSP patients had significantly lower LOS scores in FW, BW, RT, FW-RT, BW-RT and BW-LT directions compared to controls. However the scores in LT and FW-LT did not differ significantly. ConclusionsPSP patients showed impaired balance indices and decreased overall LOS compared to controls. Though LOS is affected in PSP, the scores in the left (non-dominant side) and forward-left (non-dominant forward diagonal) directions were preserved.

Morphometric analysis of subcortical structures in progressive supranuclear palsy: In vivo evidence of neostriatal and mesencephalic atrophy

Progressive supranuclear palsy (PSP) is a neurodegenerative disease characterized by gait and postural disturbance, gaze palsy, apathy, decreased verbal fluency and dysexecutive symptoms, with some of these clinical features potentially having origins in degeneration of frontostriatal circuits and the mesencephalon. This hypothesis was investigated by manual segmentation of the caudate and putamen on MRI scans, using previously published protocols, in 15 subjects with PSP and 15 healthy age-matched controls. Midbrain atrophy was assessed by measurement of mid-sagittal area of the midbrain and pons. Shape analysis of the caudate and putamen was performed using spherical harmonics (SPHARM-PDM, University of North Carolina). The sagittal pons area/midbrain area ratio (P/M ratio) was significantly higher in the PSP group, consistent with previous findings. Significantly smaller striatal volumes were found in the PSP group — putamina were 10% smaller and caudate volumes were 17% smaller than in controls after controlling for age and intracranial volume. Shape analysis revealed significant shape deflation in PSP in the striatum, compared to controls; with regionally significant change relevant to frontostriatal and corticostriatal circuits in the caudate. Thus, in a clinically diagnosed and biomarker-confirmed cohort with early PSP, we demonstrate that neostriatal volume and shape are significantly reduced in vivo. The findings suggest a neostriatal and mesencephalic structural basis for the clinical features of PSP leading to frontostriatal and mesocortical-striatal circuit disruption.

Endoscopic characteristics and levodopa responsiveness of swallowing function in progressive supranuclear palsy

Dysphagia is a frequent and early symptom in progressive supranuclear palsy (PSP) predisposing patients to aspiration pneumonia. Fiberoptic endoscopic evaluation of swallowing (FEES) has emerged as a valuable apparative tool for objective evaluation of neurogenic dysphagia. This is the first study using FEES to investigate the nature of swallowing impairment in PSP. Eighteen consecutive PSP patients (mean age 69.7 +/- 9.0 years) were included. The salient findings of FEES in PSP patients were compared with those of 15 patients with Parkinson's disease (PD). In 7 PSP patients, a standardized FEES protocol was performed to explore levodopa (L-dopa) responsiveness of dysphagia. Most frequent abnormalities detected by FEES were bolus leakage, delayed swallowing reflex, and residues in valleculae and piriformes. Aspiration events with at least one food consistency occurred in nearly 30% of PSP patients. Significant pharyngeal saliva pooling was observed in 4 PSP patients. We found no difference of salient endoscopic findings between PSP and PD patients. Endoscopic dysphagia severity in PSP correlated positively with disease duration, clinical disability, and cognitive impairment. No correlation was found with dysarthria severity. In early PSP patients, swallowing dysfunction was solely characterized by liquid leakage with the risk of predeglutitive aspiration during the oral phase of swallowing. Two PSP patients showed relevant improvement of swallowing function after L-dopa challenge. Chin tuck-maneuver, hard swallow, and modification of food consistency were identified as the most effective therapeutic interventions. In conclusion, FEES assessment can deliver important findings for the diagnosis and refined therapy of dysphagia in PSP patients.

Hyposmia in progressive supranuclear palsy

Previous studies suggested that olfaction is normal in progressive supranuclear palsy (PSP). We applied the University of Pennsylvania Smell Identification Test (UPSIT) to 36 patients with PSP who scored more than 18 on the Mini Mental State Examination (MMSE), 140 patients with nondemented Parkinson's disease (PD) and 126 controls. Mean UPSIT scores in PSP were lower than in controls (P < 0.001) but higher than in PD (P < 0.001) after adjusting for age, gender, and smoking history. For patients with PSP, UPSIT scores correlated with MMSE (r = 0.44, P = 0.006) but not disease duration (P = 0.6), motor subscale of the Unified Parkinson's Disease Rating Scale (P = 0.2), or Frontal Assessment Battery (P = 0.5). The brains of six of the patients with PSP were examined postmortem and all revealed neurofibrillary tangles and tau accumulation in the rhinencephalon, although only three had hyposmia. Further prospective studies including patients with early PSP and PSP-P with postmortem confirmation might help clarify if smell tests could be useful when the differential diagnosis lies between PD and PSP.

Differentiation of PA from early PSP with different patterns of symptoms and CBF reduction

Objective: To clarify the features of pure akinesia (PA) and progressive supranuclear palsy (PSP) in the early stage of disease.Methods: We investigated 15 PA and 41 PSP patients' clinical and radiologic features including head MRI, ethyl cysteinate dimmer-single photon emission-computed tomography (ECD-SPECT) and iodine-123 meta-iodobenzyl guanidine (123I-MIBG) myocardial scintigraphy. In ECD-SPECT study, cerebral blood flow (CBF) reduction was quantitatively expressed as Z-score, and that in the frontal lobe was evaluated.Results: Many PSP patients claimed falls as the initial symptom but no PA patients did. Eye movement, as well as optokinetic nystagmus elicitation, was more frequently disturbed in PSP. Dementia, dysarthria and rigidity were also more frequent in PSP than in PA. Midbrain tegmentum atrophy in head MRI was more frequently observed in PSP. CBF in the frontal lobe, especially in the frontal eye field, was significantly lower in PSP than in PA. MIBG myocardial scintigraphy showed no difference between two groups.Discussion: PA and PSP show distinct symptoms from the early stage, indicating that they are distinct disorders. The occurrence of falls and eye movement disturbance, as well as CBF reduction at the frontal eye field, is very important for distinguishing these disorders.

MR imaging of brainstem atrophy in progressive supranuclear palsy

To enhance the sensitivity and specificity of the clinical diagnosis of progressive supranuclear palsy (PSP), neuroradiological parameters established in pathologically proven cases are needed. We examined brainstem atrophy in five pathologically confirmed PSP patients (three men, mean age at death 77 years, range 64-84 years). Time interval between symptom onset and MRI ranged from 1 to 5 years, and between MRI and death from 33 to 52 months. Only one patient had clinical diagnosis of PSP at the time of MRI. Control group consisted of 19 age- and gender-matched healthy subjects. Seventeen morphometric parameters of the midbrain and pons were measured on T1-weighted midsagittal and T2-weighted axial MRI scans with Image Analyzer. Measurements of superior cerebellar peduncle (SCP) width were performed on PSP autopsy specimens. Mean SCP width on MRI in PSP (2.7 +/- 0.8 mm, 95%CI: 2.1-3.3) was smaller than in controls (3.7 +/- 0.5 mm, 95%CI: 3.5-3.9). Mean SCP width at autopsy was 8% smaller than mean SCP width on MRI. Midsagittal midbrain area in PSP (99.1 +/- 6.9 mm(2), 95%CI: 90.5-107.6) was smaller than in controls (141.0 +/- 18.1 mm(2), 95%CI: 132.2-149.7). Midbrain/pons area ratio in PSP was 1:5 and in controls was 1:4 (p < 0.01). Repeat MRI 17 months later in one PSP case revealed 30% decrease of SCP width. MR imaging with quantitative analysis may be useful in the diagnosis of early PSP and in monitoring disease course.