Diagnosis Of Progressive Supranuclear Palsy Research Articles

An autopsied case of progressive supranuclear palsy, initially diagnosed as spinocerebellar degeneration with severe olivopontocerebellar involvement

A Japanese female patient presented with dysarthria and gait disturbance with ataxia at the age of 63. She was initially diagnosed with spinocerebellar degeneration because a head CT showed atrophy of the cerebellum and brainstem, and dilatation of the fourth ventricle. Symptoms including abnormal behavior, dementia, vertical gaze palsy, dysphagia, retrocollis, axial rigidity, grasp reflex and positive Babinski's sign were gradually observed. Tegmental atrophy of the brainstem and dilatation of the third ventricle were apparent on images. The diagnosis was modified to progressive supranuclear palsy (PSP), 6 years after the onset of symptoms. Gastrostomy and tracheotomy were performed 7 and 8 years after onset, respectively, and the patient died one year later. At autopsy the brain weighed 1,030g and showed atrophy of the frontal lobe and cerebellum. The brainstem was also atrophic, particularly in the tegmentum and pontine base. Neurofibrillary tangles, mainly globose-type, were widespread in the subcortical structure, particularly in the globus pallidus, subthalamic nucleus, nucleus of the oculomotor nerve, substantia nigra, locus ceruleus, pontine nucleus, and the inferior olivary nucleus. Numerous glial fibrillary tangles and argyrophilic threads were also observed particularly in the frontal lobe, basal ganglia, brainstem and cerebellar white matter. The cerebellar dentate nucleus showed neuron loss with grumose degeneration and the Purkinje neuron layer showed neuron loss and Bergmann's gliosis with torpedoes. Tau positive inclusions in the Purkinje neurons, Bergmann glias and dentate nucleus neurons were observed. Pathological findings were consistent with the diagnosis of PSP but the olivopontocerebellar involvement and the quantity of Gallyas-positive/tau-positive structures were generally more severe than in typical PSP cases. According to these clinicopathologic findings and a review of the literature, we speculate on the existence of a PSP subtype with severe olivopontocerebellar involvement that tends to be clinically misdiagnosed as spinocerebellar degeneration.

The diagnosis of neurodegenerative disorders based on clinical and pathological findings using an MRI approach

Diffusion tensor imaging and voxel based morphometry are efficient in the diagnosis of neurodegenerative disorders, however, these technologies are available at a limited number of facilities. Thus, conventional MRI remains important in the diagnosis of neurodegenerative disorders. Dorsolateral putaminal hyperintensity (DPH) and hot cross bun sign discriminate Parkinson's disease from multiple system atrophy (MSA). However, differences in magnetic field strength and sequence affect the sensitivity of DPH, and mild DPH may be observed in normal elderly subjects. Patients with progressive supranuclear palsy (PSP) presenting Richardson's syndrome show midbrain tegmentum atrophy, but Parkinsonian PSP (PSP-P) and pure akinesia with gait freezing, which are other phenotypes of PSP, may not show especially during early course of illness. In patients with corticobasal degeneration (CBD), asymmetrical cerebral atrophy corresponding with corticobasal syndrome (CBS) may be a characteristic finding. However, at autopsy, CBS patients presenting asymmetrical cerebral atrophy have CBD as the underlying pathology in approximately 50% of PSP patients. The sensitivity and specificity of MRI for the diagnosis of MSA, PSP, and CBD is based generally on clinical diagnostic criteria. Diagnosis based on MRI has limitations, and, therefore, we should reconsider our diagnoses, particularly during the early course of illness.

Magnetic resonance imaging in progressive supranuclear palsy

Progressive supranuclear palsy (PSP) is a tauopathy, presenting clinically most often with a symmetrical akinetic-rigid syndrome, postural instability, supranuclear gaze palsy and frontal dementia. In the absence of reliably validated biomarkers, the diagnosis of PSP in vivo is presently based on clinical criteria, which to date do not include supporting imaging findings, as is accepted for other neurodegenerative diseases. However, data from conventional magnetic resonance imaging (MRI) and various advanced MRI techniques including magnetic resonance volumetry, voxel-based morphometry, diffusion-weighted and diffusion-tensor imaging, magnetization transfer imaging and proton resonance spectroscopy suggest that MRI can contribute valuable information for the differential diagnosis of PSP. We review here the presently published literature concerning MRI in PSP and discuss the potential role of MRI in differentiating PSP from other parkinsonian syndromes.

Diagnosis of progressive supranuclear palsy: can measurement of tau forms help?

Recently, a new assay for the differential diagnosis of progressive supranuclear palsy (PSP) was proposed. It was shown that the ratio of 33/55 kDa tau forms in cerebrospinal fluid (CSF) was specifically reduced in PSP CSF. We aimed to reproduce these results, but were not able to detect the tau forms in CSF. We demonstrate that i) CSF total tau levels are too low to be detected by the published protocol, and ii) the described 33 and 55 kDa bands are likely the heavy and light chains of IgG used in the assay. We conclude that more sensitive techniques are needed to measure tau forms in CSF.

A Combination of CSF Tau Ratio and Midsaggital Midbraintopons Atrophy for the Early Diagnosis of Progressive Supranuclear Palsy

Cerebrospinal fluid (CSF) tau ratio decrease (33kDa/55kDa forms) and mid-saggital midbrain-to-pons (MP) atrophy have been suggested as diagnostic markers for progressive supranuclear palsy (PSP). The usefulness of their combined evaluation has never been tested. We evaluated the CSF tau ratio and the MP atrophy as a combined marker for early identification of PSP. A total of 87 subjects, namely 18 PSP, 25 controls (CON), 16 corticobasal syndrome (CBS), and 28 frontotemporal dementia (FTD), were included. Each subject underwent a lumbar puncture and a conventional MRI scan to assess CSF tau 33 kDa/55 kDa ratio and mid-saggital MP measure, respectively. CSF tau ratio and MP ratio were significantly reduced in PSP patients when compared to CON, CBS, and FTD (p< 0.001). Data-based "optimal" combination of CSF tau ratio and MP measure was defined, and the combined marker TrMp= sqrt[3]{CSF Tau ratio}} × {MP ratio} was considered. Considering the combined marker, the difference between the area under the curve (dAUC) of the receiver operating characteristic analysis in PSP versus the various subgroups was higher by about 10% than that obtained by each marker individually. In PSP versus others, a proposed "best" cut-off of TrMP = 0.182 resulted in 94.2% sensitivity and 84.0% specificity. When patients with onset of symptoms ≤ 2 years were included, TrMP resulted significantly decreased in PSP compared to CBS (p< 0.001) and FTD (p< 0.001). The combined marker increases the discriminative power in identifying PSP and suggests that the interplay of different markers should be considered in future trials to enhance diagnostic accuracy from the early stages.

Diagnostic accuracy of the magnetic resonance Parkinsonism index and the midbrain‐to‐pontine area ratio to differentiate progressive supranuclear palsy from Parkinson's disease and the Parkinson variant of multiple system atrophy

Using magnetic resonance (MR) planimetry, both the midbrain-to-pontine area ratio (m/p-ratio) and the MR parkinsonism index (MRPI) have been shown to assist in the differential diagnosis of progressive supranuclear palsy (PSP) from Parkinson's disease (PD) and the Parkinson variant of multiple system atrophy (MSA-P). The aim of this study was to determine the diagnostic accuracy of the MRPI compared with the m/p-ratio in a large cohort of 123 patients with neurodegenerative parkinsonism including patients with PSP, PD, and MSA-P. Patients with PSP had significant higher MRPI values and significant smaller m/p-ratios compared with the other groups with overlapping individual values. Overall predictive accuracy was similar for the m/p-ratio (87.0%) and the MRPI (80.5%) with a predictive accuracy for PSP from MSA-P being significantly better for the MRPI (87.5%) compared with the m/p-ratio (75%) as well as a predictive accuracy for PSP from PD being significantly better for the m/p-ratio (87.6%) compared with the MRPI (77.3%). Both the m/p-ratio and the MRPI may assist the clinical differential diagnosis in neurodegenerative parkinsonism.

Acoustical Analysis of Speech in Progressive Supranuclear Palsy

Dysarthria often is an early and prominent clinical feature of progressive supranuclear palsy (PSP). Based on perceptual analyses, speech impairment in PSP reportedly consists of prominent hypokinetic and spastic components with occasional ataxic features. To measure objectively and quantitatively different speech parameters in PSP as compared with Parkinson's disease (PD) by acoustical analysis and to correlate these parameters with disease duration, global motor, and speech impairment and with the subtype of disease (Richardson's syndrome [RS] vs parkinsonian type of PSP [PSP-P]). Twenty-six patients with clinical diagnosis of PSP (n=14 classified as RS and n=12 classified as PSP-P) and 30 age- and gender-matched patients with clinical diagnosis of PD were tested. Speech examination was based on the acoustical analysis of a standardized four-sentence reading task. Several speech variables were measured to assess phonation, intonation variability, speech velocity, and articulatory precision. All participants were tested according to Unified Parkinson's Disease Rating Scale/Motor Score (UPDRS-III) and staged according to Hoehn and Yahr stages. Global speech intelligibility was evaluated on the basis of the UPDRS-III speech item. In the PSP group, speech velocity, intonation variability, and the fraction of intraword pauses as a measure of articulatory precision were significantly reduced, whereas the percentage of speech pauses was prolonged as compared with the PD group. Only in the male PSP patients, vowel articulation was found to be impaired. Global speech performance was worse in the PSP group in comparison with the PD group and showed a correlation to some distinct speech dimensions. No differences of speech variables were seen between RS and PSP-P patients. PSP patients feature a mixed type of dysarthria with hypokinetic and spastic components that differ significantly from the speech performance of PD speakers. This probably reflects the widespread neuropathological changes in PSP comprising basal ganglia as well as pontine and further brainstem regions.

The Brainstem: Anatomy, Assessment, and Clinical Syndromes

Cover and Figure 1. The internal anatomy of the brainstem is presented in a simplified, color-coded format. Cover. The approximate locations and extents of nuclei that are important sources for a particular neurotransmitter are colorcoded onto a sagittal magnetic resonance image. Figure 1. The approximate locations and extent of major tracts and nuclei are colorcoded onto simplified axial illustrations of brainstem sections (left panel). The most common pattern of arterial territories is also presented (right panel). All illustrations are oriented in the radiographic perspective.

Erhöhte Frequenzanteile < 0,1 Hertz aus der Posturografie differenzieren zwischen der Progressiven Supranukleären Blickparese und dem idiopathischen Parkinson-Syndrom

Hintergrund Die posturale Instabilität zählt zu den Kardinalsymptomen bei den Parkinson-Syndromen. Treten frühzeitig Stürze und Gleichgewichtsprobleme im Rahmen eines Parkinson-Syndroms auf, ist eine differenzialdiagnostische Reevaluierung mit Verdacht auf eine progressive supranukleäre Blickparese (PSP) zu überdenken. Methodik Es wurden Weg-Zeit-Parameter, die Schwankungsflächenradien und die Frequenzleistungen (0,00–3,00 Hz) von 6 wahrscheinlichen PSP-Patienten mit 20 idiopathischen Parkinson-Patienten und einer altersgleichen Kontrollgruppe mittels statischer Posturografie (Kraftmessplatte ADDON®) beim Stehen über 20 Sekunden in den Bedingungen „Augen offen” (AO) und „Augen geschlossen” (AG) verglichen. Ergebnisse Die PSP-Gruppe unterscheidet sich bezüglich der Standleistung signifikant von der Kontrollgruppe und der IPS-Gruppe (Schwankungsflächenradius: F2,43 = 10,52; p = 0,000) unabhängig der visuellen Afferenz mit signifikant erhöhten Signalanteile im Frequenzteilspektrum 0,00–0,05 Hz in anterior / posteriore Richtung (A / P) und medio / laterale Richtung (M / L) (AO M / L: F2,43 = 8,01; p = 0,001; AO A / P: F2,43 = 6,73; p = 0,003; AG M / L: F2,43 = 11,09; p = 0,000; AG A / P: F2,43 = 5,73; p = 0,006). Schlussfolgerung Die Ergebnisse bestätigen einen erhöhten Schwankungsflächenbedarf der PSP-Patienten als Indikator für die hohe posturale Instabilität. PSP-Patienten weisen eine signifikant erhöhte Schwankungsfrequenz im Low-Frequenzbereich (< 1 Hz) in A / P- und M / L-Richtung auf, die mit Störungen des visuellen posturalen Subsystems korrespondieren. Mithilfe der Fast-Fourier-Analyse aus der Posturografie konnten erstmals die visuellen Störungen der PSP-Patienten als möglicher differenzialdiagnostischer Marker zwischen IPS und PSP identifiziert werden.

Familial aggregation of parkinsonism in progressive supranuclear palsy

Progressive supranuclear palsy (PSP) is a progressive neurodegenerative disorder characterized by aggregates of the microtubule-associated protein tau (MAPT). A nonsignificant trend for positive family history has been observed in two case-control studies and several pedigrees with familial clustering of parkinsonism have been described. Occasionally, mutations in MAPT are found in patients with a clinical phenotype similar to PSP. In this case-control study, we compared the occurrence of dementia and parkinsonism among first-degree relatives of patients with PSP with an age- and sex-matched control group. Family history of dementia and parkinsonism was collected from all first-degree relatives of patients with PSP who fulfilled the international National Institute of Neurological Disorders and Stroke criteria for PSP. Age- and sex-matched controls were selected from the Rotterdam Study. Genetic testing and pathologic examination was performed in a subset of familial PSP cases. Fifty-seven (33%) of the 172 patients with PSP had at least one first-degree relative who had dementia or parkinsonism compared to 131 (25%) of the control subjects (odds ratio [OR] 1.5, 95% confidence interval [CI] 1.01-2.13). In patients with PSP, more first-degree relatives with parkinsonism were observed compared to controls, with an OR 3.9 (95% CI 1.99-7.61). Twelve patients with PSP (7%) fulfilled the criteria for an autosomal dominant mode of transmission. The intrafamilial phenotype within these pedigrees varied among PSP, dementia, tremor, and parkinsonism. Genetic studies revealed one patient with a P301L mutation in MAPT. Pathologic examination of five familial cases confirmed the clinical diagnosis of PSP, with predominant four repeat tau pathology in affected brain areas. This study demonstrates familial aggregation of parkinsonism in progressive supranuclear palsy.

Parkinsonism, dysautonomia, REM behaviour disorder and visual hallucinations mimicking synucleinopathy in a patient with progressive supranuclear palsy

Strict application of diagnostic criteria and diagnosis reassessment during follow-up have reduced the clinicopathological dissociation in the field of movement disorders. After several clinicopathological studies, dysautonomia, REM behaviour disorder (RBD)...

Automated Computer Differential Classification in Parkinsonian Syndromes via Pattern Analysis on MRI

Reported error rates for initial clinical diagnosis of idiopathic Parkinson's disease (IPD) against other Parkinson Plus Syndromes (PPS) can reach up to 35%. Reducing this initial error rate is an important research goal. We evaluated the ability of an automated technique, based on structural, cross-sectional T1-weighted (T1w) magnetic resonance imaging, to perform differential classification of IPD patients versus those with either progressive supranuclear palsy (PSP) or multiple systems atrophy (MSA). A total of 181 subjects were included in this retrospective study: 149 healthy controls, 16 IPD patients, and 16 patients diagnosed with either probable PSP (n = 8) or MSA (n = 8). Cross-sectional T1w magnetic resonance imagers were acquired and subsequently corrected, scaled, resampled, and aligned within a common referential space. Tissue composition and deformation features in the hindbrain region were then automatically extracted. Classification of patients was performed using a support vector machine with least-squares optimization within a multidimensional composition/deformation feature space built from the healthy subjects' data. Leave-one-out classification was used to avoid over-determination. There were no age difference between groups. The automated system obtained 91% accuracy (agreement with long-term clinical follow-up), 88% specificity, and 93% sensitivity. These results demonstrate that a classification approach based on quantitative parameters of three-dimensional hindbrain morphology extracted automatically from T1w magnetic resonance imaging has the potential to assist in the differential diagnosis of IPD versus PSP and MSA with high accuracy, therefore reducing the initial clinical error rate.

Diffusion-weighted brain imaging study of patients with clinical diagnosis of corticobasal degeneration, progressive supranuclear palsy and Parkinson's disease

Corticobasal degeneration (CBD) and progressive supranuclear palsy (PSP) are two neurodegenerative disorders within the category of tauopathies, which must be considered in differential diagnosis of Parkinson's disease. Although specific clinical and neuroradiological features help to guide the clinician to a likely diagnosis of Parkinson's disease, CBD or PSP, differential diagnosis remains difficult. The aim of our study was to analyse apparent diffusion coefficient (ADC(ave)) maps from patients with clinical diagnosis of CBD (corticobasal syndrome, CBS), classical phenotype of PSP (Richardson's syndrome, RS) and Parkinson's disease (PD) in order to identify objective markers to discriminate between these groups. Thirteen Parkinson's disease patients, 10 RS patients, 7 CBS patients and 9 healthy volunteers were recruited and studied in a 1.5 T MR scanner. Axial diffusion-weighted images were obtained and the ADC(ave) map was generated. Regions of interest (ROIs) included mesencephalon, corpus callosum and left and right superior cerebellar peduncle (SCP), thalamus, caudate, putamen, pallidus, posterior limb of internal capsule, frontal and parietal white matter. Histograms of ADC(ave) were generated for all voxels in left and right cerebral hemispheres and in left and right deep grey matter regions separately, and the 50th percentile values (medians) were determined. The ratio of the smaller to the larger median value (symmetry ratio) was calculated for left and right hemispheres and for left and right deep grey matter regions (1 = perfect symmetry). Putaminal ADC(ave) values in CBS and RS were significantly greater than those in Parkinson's disease and healthy volunteers, but could not distinguish CBS from RS patients. In CBS patients, the values of the medians of cerebral hemispheres histograms were significantly higher than those in RS, Parkinson's disease and healthy volunteers, while the hemispheric symmetry ratio in CBS (0.968, range 0.952-0.976) was markedly reduced compared with RS (0.993, range 0.992-0.994), Parkinson's disease (0.991, range 0.988-0.993) and healthy controls (0.990, range 0.988-0.993). The hemispheric symmetry ratio differentiated CBS patients from RS and Parkinson's disease patients with a sensitivity and specificity of 100%. In RS patients, the ADC(ave) values of the SCPs were significantly greater than those in Parkinson's disease and healthy volunteers. Our findings confirm that putaminal ADC(ave) values evaluation provides a good discrimination between Parkinson's disease and atypical parkinsonisms, including RS and CBS. Furthermore, diffusion-weighted imaging, by detecting the brain microstructural correlates of the typical asymmetric signs and symptoms in CBS and the SCP involvement in RS, was shown to aid characterization and differentiation of atypical parkinsonism.

Apparent diffusion coefficient of the superior cerebellar peduncle differentiates progressive supranuclear palsy from Parkinson's disease

The early diagnosis of progressive supranuclear palsy (PSP) may be challenging, because of clinical overlapping features with Parkinson's disease (PD) and other parkinsonian syndromes such as the Parkinsonian variant of multiple system atrophy (MSA-P). Conventional MRI can help in differentiating parkinsonian disorders but its diagnostic accuracy is still unsatisfactory. On the basis of the pathological demonstration of superior cerebellar peduncle (SCP) atrophy in patients with PSP, we assessed the SCP apparent diffusion coefficient (ADC) values in patients with PSP, PD, and MSA-P in order to evaluate its differential diagnostic value in vivo. Twenty-eight patients with PSP (14 with possible-PSP and 14 with probable-PSP), 15 PD, 15 MSA-P, and 16 healthy subjects were studied by using diffusion weighted imaging (DWI). ADC was calculated in regions of interest defined in the left and right SCP by two clinically blinded operators. Intrarater (r = 0.98, P < 0.001) and interrater reliability (r = 0.97; P < 0.001) for SCP measurements were high. Patients with PSP had higher SCP rADC values (median 0.98 x 10(-3)mm(2)/s) than patients with PD (median 0.79 x 10(-3) mm(2)/s, P < 0.001), MSA-P (median 0.79 x 10(-3) mm(2)/s, P < 0.001), and healthy controls (median 0.80 x 10(-3) mm(2)/s, P < 0.001). DWI discriminated patients with PSP from PD and healthy subjects on the basis of SCP rADC individual values (100% sensitivity and specificity) and from patients with MSA-P (96.4% sensitivity and 93.3% specificity). The higher values of rADC in SCP of patients with PSP correspond with the in vivo microstructural feature of atrophy detected postmortem and provide an additional support for early discrimination between PSP and other neurodegenerative parkinsonisms.

Autonomic dysfunction in patients with progressive supranuclear palsy

The most important features that characterize and differentiate progressive supranuclear palsy (PSP) from other parkinsonian syndromes are postural instability, supranuclear gaze palsy, pseudobulbar palsy, and cognitive disturbances. Although it has been reported that significant autonomic dysfunction is an exclusionary feature for PSP diagnosis, we could demonstrate in this study using semiquantitative clinical interview and cardiovascular testing that both PSP and idiopathic Parkinson's disease (PD) patients can present with significant autonomic dysfunction. The parasympathetic cardiovascular system seems to be involved to a similar extent in PD and PSP patients, whereas sympathetic cardiovascular dysfunction is more frequent and severe in PD patients, but can also be found in PSP patients. Our findings have a profound implication on the diagnosis and treatment of PSP patients.

Diffusion tensor analysis of corpus callosum in progressive supranuclear palsy

Progressive supranuclear palsy (PSP) is a neurodegenerative disease featuring parkinsonism, supranuclear ophthalmoplegia, dysphagia, and frontal lobe dysfunction. The corpus callosum which consists of many commissure fibers probably reflects cerebral cortical function. Several previous reports showed atrophy or diffusion abnormalities of anterior corpus callosum in PSP patients, but partitioning method used in these studies was based on data obtained in nonhuman primates. In this study, we performed a diffusion tensor analysis using a new partitioning method for the human corpus callosum. Seven consecutive patients with PSP were compared with 29 age-matched patients with Parkinson's Disease (PD) and 19 age-matched healthy control subjects. All subjects underwent diffusion tensor magnetic resonance imaging, and the corpus callosum was partitioned into five areas on the mid-sagittal plane according to a recently established topography of human corpus callosum (CC1-prefrontal area, CC2-premotor and supplementary motor area, CC3-motor area, CC4-sensory area, CC5-parietal, temporal, and occipital area). Fractional anisotropy (FA) and apparent diffusion coefficient (ADC) were measured in each area and differences between groups were analyzed. In the PSP group, FA values were significantly decreased in CC1 and CC2, and ADC values were significantly increased in CC1 and CC2. Receiver operating characteristic analysis showed excellent reliability of FA and ADC analyses of CC1 for differentiating PSP from PD. The anterior corpus callosum corresponding to the prefrontal, premotor, and supplementary motor cortices is affected in PSP patients. This analysis can be an additional test for further confirmation of the diagnosis of PSP.

Astrocytic tau pathology positively correlates with neurofibrillary tangle density in progressive supranuclear palsy

Tufted astrocytes (TAs) are considered reliable, specific markers for the neuropathologic diagnosis of progressive supranuclear palsy (PSP). It is known that neurofibrillary tangles (NFTs) may relate directly to neurodegeneration, but the role of glial tau pathology is not well determined. To examine the hypothesis that TAs are as pathogenic as NFTs and that both might have a common accumulation, we evaluated the topographic relationship between TAs and NFTs in 12 cases of PSP. The sections of 13 different parts of the brain were stained using the Gallyas-Braak method, and TAs and NFTs were counted and compared statistically. The number of TAs significantly correlated with that of NFTs in the central gray matter, pontine nuclei, and tegmentum, which are responsible for the main symptoms in PSP. In the examined allocortex, however, NFTs were abundant without accompanying TAs. Staining with the specific antibody for 4-repeat tau (RD4) and 3-repeat tau (RD3) was performed to clarify this discrepancy from the standpoint of tau isoforms. NFTs in the entorhinal cortex were stained with both RD3 and RD4, but NFTs in the premotor cortex were stained with only RD4. The nature of NFTs in the allocortical area was different from that of the isocortex in PSP. TAs in the isocortex may share the same pathologic cascade with NFTs stained only by RD4. These results suggest that TAs are part of the same pathologic process as NFTs in PSP.

Pure akinesia as initial presentation of PSP: A clinicopathological study

Pure akinesia (PA) is a rare neurodegenerative condition that may represent a limited expression of progressive supranuclear palsy (PSP). Only a few pathological studies have been reported and its classification remains unclear. We report the case of a 57-year-old Caucasian man who was initially clinically diagnosed with classical PA. After four years the patient developed additional symptoms and signs compatible with the diagnosis of clinically probable PSP. The diagnosis of PSP was confirmed by post-mortem examination. Genetic analysis of the MAPT gene revealed an A0/A0 genotype, which has been repeatedly associated with the PSP phenotype, and might discriminate between PA and other gait disorders. Our case strengthens the hypothesis that PA should be considered as initial manifestation of PSP.

Differential diagnostic value of eye movement recording in PSP-Parkinsonism, Richardson's Syndrome, and Idiopathic Parkinson's Disease

Objectives: Vertical gaze palsy is a highly relevant clinical sign in Parkinsonian syndromes. As the eponymous feature it is one of the core features in the diagnosis of progressive supranuclear palsy (PSP). Recent studies have suggested a further differentiation of PSP in Richardson's Syndrome (RS) and PSP-Parkinsonism (PSP-P). The aim of this study was to search for oculomotor abnormalities in the PSP-P subset out of a sample of PSP patients and to compare these findings with those of RS patients, patients with Idiopathic Parkinson's disease (IPD) and a control group.

The auditory startle response in parkinsonism may reveal the extent but not type of pathology

We measured the acoustic startle response (ASR) and blink reflex (ABR) in patients with clinically diagnosed Parkinson's disease (PD) and progressive supranuclear palsy (PSP) and determined the specificity of an abnormal result for the diagnosis of PSP. Thirty patients (11 PD, 19 PSP) and 12 age matched controls were studied. The PSP group was separated into clinical subgroups. Fourteen patients with early falls, cognitive dysfunction and eye movement abnormalities were classified as Richardson's disease (RD), 3 with parkinsonism in the absence of early falls, cognitive dysfunction or eye movement abnormalities were classified PSP-parkinsonism (PSP-P) and 2 who presented with gait unsteadiness and freezing without cognitive dysfunction or eye movement abnormalities were classified as pure akinesia with gait freezing (PAGF). Following an acoustic startle stimulus EMG activity was recorded in the orbicularis oculi and sternomastoid muscles. The likelihood ratio of an absent response being clinically diagnosed PSP was determined. The ABR was present in 11/19 (58%) of patients with PSP, and 11/11 with PD and 12/12 controls (H2 p < 0.05). The ASR measured at the sternomastoid was present in only 2/19 (11%) of patients with PSP, but in 5/11 (45%) with PD and 6/12 (50 %) controls (H2 p < 0.05). The ABR was present in only 6/14 (43%) of the RD group, but in 3/3 PSP-P and 2/2 PAGF. Loss of the ABR was 100% specific for PSP, but only 42 % sensitive. Loss of the sternomastoid ASR had a likelihood ratio of 1.9 for the clinical diagnosis of PSP. The ASR and ABR appear unlikely to be useful in differentiating PSP from PD. Abnormalities in these responses are worse in RD where the pathology is known to be more widespread than in PSP-P and PAGF.