Clinical Diagnosis Of Progressive Supranuclear Palsy Research Articles

Low Clinical Sensitivity and Unexpectedly High Incidence for Neuropathologically Diagnosed Progressive Supranuclear Palsy (PSP) (S51.001)

Low Clinical Sensitivity and Unexpectedly High Incidence for Neuropathologically Diagnosed Progressive Supranuclear Palsy (PSP) (S51.001)

Dysphagia in progressive supranuclear palsy: A scoping review protocol

BACKGROUND: One of the most prevalent types of atypical Parkinsonian syndrome is progressive supranuclear palsy (PSP). PSP is associated with early onset of dysphagia which can result in malnutrition, dehydration, and aspiration pneumonia, affecting quality of life and increasing mortality rate. To date, research describing dysphagia in PSP and its impact is scant. OBJECTIVE: The objective of this scoping review is to determine the characteristics of dysphagia in PSP, differences in dysphagia presentation according to PSP subtype, principal methods used for identifying and diagnosing dysphagia and the impact dysphagia has on quality of life in individuals with PSP. METHODS: The proposed scoping review will be conducted in accordance with the JBI methodology for scoping reviews. The Preferred Reporting Items for Systematic Reviews and Meta Analysis extension for scoping reviews (PRISMA-ScR) will be used to guide the reporting of the review (Tricco et al., 2018). Articles completed at any time, which include participants with dysphagia and a clinical diagnosis of PSP will be included. Studies involving participants who have a co-morbidity/morbidities which could cause dysphagia and secondary research will be excluded. Relevant electronic databases, trial registries and grey literature without any date or language restrictions will be searched. Two independent reviewers will assess articles for eligibility and will extract relevant data. CONCLUSIONS: This scoping review will provide important evidence on dysphagia and PSP. It will describe the principal methods used for identifying and diagnosing dysphagia in this population. The results will guide future research in dysphagia and PSP.

Idiopathic normal pressure hydrocephalus-like MRI features in patients with progressive supranuclear palsy: a comparative case-control study

ABSTRACT Background The occurrence of neurodegenerative disease in patients with normal pressure hydrocephalus (NPH) is emphasized in recent reports. Based on this common co-occurrence, some of the hydrocephalic disorders appearing in late adulthood have been hypothesized to result from initially unapparent parenchymal abnormalities of neurodegenerative origin. Among these diseases, progressive supranuclear palsy (PSP) has been specifically remarked on. We aimed to comparatively investigate the neuroimaging clues of iNPH in our PSP subjects. Methods Eighteen patients with a clinical diagnosis of PSP, 44 with Parkinson’s disease (PD), and 44 healthy control (HC) individuals were enrolled. The disproportionately enlarged subarachnoid space hydrocephalus (DESH) score, the Evans’ index (EI), and the callosal angle (CA) were measured on the conventional magnetic resonance imaging (MRI). The comparative analyses were performed using IBM SPSS Statistics 26. Results We found that dilated Sylvian fissures score (p = 0.016) and focal sulcal dilatation score (p = 0.037) were higher in the PSP group in comparison to HC whereas the CA score was higher in PSP subjects in comparison to both PD patients and HC (p = 0.000). Remarkably, the DESH score was also found to be higher in the PSP group in comparison to the age-matched HC group (p = 0.024). Conclusions We found that the NPH-like MRI features were more common in PSP subjects in comparison to PD subjects and age-matched HC. These results may provide critical contributions to the literature regarding the overlap between PSP and NPH.

A cerebrospinal fluid microRNA analysis: Progressive supranuclear palsy.

Progressive supranuclear palsy (PSP) is a neurodegenerative tauopathy described as a syndrome of postural instability, supranuclear vertical gaze palsy, dysarthria, dystonic rigidity of the neck and trunk, dementia, and pseudobulbar palsy. The clinical diagnosis of PSP is often difficult because there are no established biomarkers, and diagnosis is currently based on clinical and imaging findings. Furthermore, the etiology and pathogenesis of PSP remain unknown. Dysregulation of microRNAs (miRNAs/miRs) has been reported to serve an important role in neurodegenerative diseases. However, the miRNA profiles of patients with PSP are rarely reported. The present study aimed to examine cerebrospinal fluid miRNAs, which are considered to be more sensitive indicators of changes in the brain, to elucidate the pathophysiology of PSP and to establish specific biomarkers for diagnosis. The present study used a microarray chip containing 2,632 miRNAs to examine cerebrospinal fluid miRNA expression levels in 11 patients with PSP aged 68–82 years. A total of 8 age- and sex-matched controls were also included. A total of 38 miRNAs were significantly upregulated and one miRNA was significantly downregulated in the cerebrospinal fluid of patients with PSP. The patients were divided into two groups based on disease stage (early onset and advanced), and changes in miRNA expression were examined. The miRNAs that were most significantly upregulated or downregulated in the early onset group were miR-204-3p, miR-873-3p and miR-6840-5p. The target genes of these miRNAs were associated with molecules related to the ubiquitin-proteasome system and autophagy pathway. Furthermore, these miRNAs were found to target genes that have been reported to have epigenetic changes following an epigenome-wide association study of brain tissues of patients with PSP. This suggested that these miRNAs and genes may have some involvement in the pathogenesis of PSP. However, the sample size of the present study was small; therefore, a greater number of patients with PSP should be examined in future studies.

The role of Alzheimer’s disease pathology in frontotemporal dementia related syndromes

AbstractBackgroundCorticobasal syndrome (CBS) and progressive supranuclear palsy (PSP) are two syndromes associated with frontotemporal lobar degeneration (FTLD) with heterogeneous presentation and progression. Co‐pathology of FTLD and Alzheimer’s disease (AD) has been described and could influence the clinical presentation of CBS and PSP. The goal of this study is to evaluate the role of AD pathology in CBS and PSP, by analyzing functional and structural neuroimaging and memory performance.MethodPatients with a clinical diagnosis of PSP and CBS (n=15) and AD (n=18) underwent functional magnetic resonance imaging (fMRI) and diffusion tensor imaging (DTI). Patients were separated according to AD biomarker positivity (CBS‐PSP‐AD, n=6) and negativity (CBS‐PSP‐noAD, n=9) based on the presence of AD biomarkers in cerebrospinal fluid. FMRI images were preprocessed to assess connectivity differences in the default mode network (DMN). DTI was analyzed to trace the bilateral superior longitudinal fasciculus (SLF) and extract its fractional anisotropy and mean diffusivity. Verbal learning and memory were assessed with the California Verbal Learning Test (CVLT‐II) and the Consortium to Establish a Registry for Alzheimer’s disease (CERAD) of the Toronto Cognitive Assessment, and the z‐scores were compared between groups.ResultThe DMN showed reduced functional connectivity in the groups with AD biomarker positivity (CBS‐PSP‐AD and AD patients) relative to the CBS‐PSP‐noAD group. Specifically, reduced connectivity was observed between the left angular gyrus and the left (T(23) = ‐4.02, p‐FDR= 0.02) and right (T(23) = ‐3.48, p‐FDR=0.04) lateral parietal regions in AD vs CBS‐PSP‐noAD. Reduced connectivity was found between the left angular gyrus, the posterior cingulate cortex (T(11) = ‐4.72, p‐FDR=0.02) and the right hippocampus (T(11) = ‐3.94, p‐FDR=0.04) in CBS‐PSP‐AD vs CBS‐PSP‐noAD. No differences were found in DMN connectivity in AD vs CBS‐PSP‐AD. SLF tractography metrics showed no difference between groups. Both CBS‐PSP‐AD and AD patients had significantly worse delayed memory scores than the CBS‐PSP‐noAD group (post‐hoc p‐FDR=0.01).ConclusionThere are similarities between AD positive biomarker groups (CBS‐PSP‐AD and AD patients) in functional connectivity and memory scores, with these groups differing from the CBS‐PSP‐noAD patients. These results suggest that pathology can mediate functional connectivity patterns and influence clinical manifestation.

Progressive supranuclear palsy often develops idiopathic normal pressure hydrocephalus-like magnetic resonance imaging features.

Idiopathic normal pressure hydrocephalus (iNPH) is a clinical entity without established pathological hallmarks. Previous autopsy studies reported that patients with an antemortem diagnosis of iNPH had a different postmortem diagnosis, commonly progressive supranuclear palsy (PSP). Disproportionately enlarged subarachnoid space hydrocephalus (DESH) has been reported as a characteristic feature of iNPH on magnetic resonance imaging (MRI). In addition, periventricular white matter hyperintensities (PVHs) are noted in most patients with iNPH; these PVHs are supposed to reflect transependymal movement of ventricular cerebrospinal fluid. It is hypothesized that PSP develops more iNPH-like MRI features than other neurodegenerative disorders. Thirty-eight patients with a clinical diagnosis of PSP, 42 with Parkinson's disease (PD) without dementia, 30 with PD with dementia (PDD) and 29 with Alzheimer's disease (AD) were enrolled. The DESH score and PVH grade were measured using the conventional MRI sequence and were compared amongst the patient groups. Disproportionately enlarged subarachnoid space hydrocephalus score was significantly higher in patients with PSP than PD without dementia, and there was a trend that the DESH score was higher in patients with PSP than PDD or Alzheimer's disease. PVH grade was significantly larger in patients with PSP than PD without dementia. In the components of the DESH score, callosal angle was significantly smaller in patients with PSP than in PD without dementia or PDD. This study demonstrated that some PSP patients develop iNPH-like MRI features, suggesting the presence of iNPH-like features in the clinical spectrum of PSP. A clinical phenotype of PSP with hydrocephalus is proposed, which should be further investigated in future studies.

Locus coeruleus pathology in progressive supranuclear palsy, and its relation to disease severity

The locus coeruleus is the major source of noradrenaline to the brain and contributes to a wide range of physiological and cognitive functions including arousal, attention, autonomic control, and adaptive behaviour. Neurodegeneration and pathological aggregation of tau protein in the locus coeruleus are early features of progressive supranuclear palsy (PSP). This pathology is proposed to contribute to the clinical expression of disease, including the PSP Richardson’s syndrome. We test the hypothesis that tau pathology and neuronal loss are associated with clinical heterogeneity and severity in PSP.We used immunohistochemistry in post mortem tissues from 31 patients with a clinical diagnosis of PSP (22 with Richardson’s syndrome) and 6 control cases. We quantified the presence of hyperphosphorylated tau, the number of pigmented cells indicative of noradrenergic neurons, and the percentage of pigmented neurons with tau-positive inclusions. Ante mortem assessment of clinical severity using the PSP rating scale was available within 1.8 (±0.9) years for 23 patients.We found an average 49% reduction of pigmented neurons in PSP patients relative to controls. The loss of pigmented neurons correlated with disease severity, even after adjusting for disease duration and the interval between clinical assessment and death. The degree of neuronal loss was negatively associated with tau-positive inclusions, with an average of 44% of pigmented neurons displaying tau-inclusions.Degeneration and tau pathology in the locus coeruleus are related to clinical heterogeneity of PSP. The noradrenergic deficit in the locus coeruleus is a candidate target for pharmacological treatment. Recent developments in ultra-high field magnetic resonance imaging to quantify in vivo structural integrity of the locus coeruleus may provide biomarkers for noradrenergic experimental medicines studies in PSP.

Midbrain area for differentiating Parkinson’s disease from progressive supranuclear palsy

ObjectivesWe aimed to investigate the values of midbrain area in diagnosing Parkinson’s Disease (PD) and progressive supranuclear palsy (PSP) by using transcranial sonography (TCS). Disease duration effect on brain sonographic findings could decrease the accuracy of TCS in PD and PSP patients. We reduced the disease duration effect on sonographic differences found between PD and PSP patients by using multivariate analysis. Patients and MethodsPatients with clinical diagnosis of PSP and PD were recruited. We used SonoSite Edge II Ultrasound system to measure midbrain area, diameter of third ventricle and substantia nigra echogenicity. Diagnostic value of each measured area in sonography was estimated regarding its power for diagnosing PD or PSP. Independent sample t-test, Regression analysis and receiver operating characteristic (ROC) curve were performed using SPSS software. ResultsOf 35 patients, 18 were PD and 17 PSP cases. The mean midbrain area was 4.86 ± 0.71cm2 in PD patients and 3.61 ± 0.85cm2 in those with PSP (P < 0.005). Regression for reducing the effect of disease duration on midbrain area variances between patients with PD and PSP revealed a significant P value (P < 0.005, Adjusted R2 = 0.36). The sensitivity and specificity of midbrain area in diagnosing PD were 83.3% and 70.6% respectively. The sensitivity of the third ventricle size in diagnosing PSP was 82% although its specificity was 62%. ConclusionMidbrain area in patients with PD was wider than those with PSP that was not affected by disease duration. Midbrain area was the most accurate index for diagnosing PD by TCS although third ventricle size was the most sensitive one for diagnosing PSP.

GBA-associated parkinsonism and dementia: beyond α-synucleinopathies?

To date the role of GBA mutations beyond α-synucleinopathies in the parkinsonism-dementia spectrum is still unclear. The aim of the study was to screen for GBA mutations in progressive supranuclear palsy (PSP), corticobasal syndrome (CBS), primary progressive aphasia (PPA) and the behavioural variant of frontotemporal dementia (bvFTD). In all, 303 patients with a clinical diagnosis of PSP (n = 157), CBS (n = 39), PPA (n = 35) and bvFTD (n = 72) and 587 neurologically healthy controls were screened for the most common GBA mutations. GBA mutations were detected in one healthy control and four patients with a clinical diagnosis of PSP (n = 1), probable CBS (n = 2) and PPA (n = 1, with concomitant C9orf72 expansion). Overall the prevalence of GBA mutations was low in non-α-synucleinopathies but significantly higher in the CBS subgroup compared to controls. Although numbers are small, our findings indicate that the clinical phenotype of GBA-associated neurodegenerative disease is more heterogeneous than previously assumed, including phenotypes not usually associated with underlying α-synucleinopathies. This may be of relevance, once causal therapeutic strategies for GBA-associated neurodegenerative disease are developed.

The phenotypic spectrum of progressive supranuclear palsy

Traditionally, the clinical picture of progressive supranuclear palsy (PSP) was defined by early postural instability with falls, supranuclear vertical gaze palsy, symmetric akinesia and rigidity, frontal and subcortical dementia, and pseudobulbar palsy, leading to death after a mean disease duration of approximately six years. A definite diagnosis of PSP depends on neuropathological confirmation. In recent years, clinico-pathological studies have drawn attention to various “atypical” clinical manifestations of PSP. In these, a clinical diagnosis of PSP is delayed or never accomplished. Comprehensive understanding of the natural history of PSP is required to permit an early and accurate diagnosis. Based on current evidence, this review provides an update on the clinical spectrum of PSP.

Impact of Aspiration Pneumonia on the Clinical Course of Progressive Supranuclear Palsy: A Retrospective Cohort Study.

IntroductionAlthough aspiration pneumonia is the most common complication of progressive supranuclear palsy (PSP), the clinical impact of aspiration pneumonia on disease course and survival has not been fully estimated. Thus, we retrospectively analyzed the prognostic factors and clinical consequences of pneumonia in PSP.MethodsThe clinical course of patients with aspiration pneumonia was surveyed. The association between baseline clinical features (2 years from disease onset) and latency to the initial development of pneumonia was investigated using survival time and Cox regression analyses.ResultsNinety patients with a clinical diagnosis of PSP were observed for 5.1±3.8 years (mean±SD), and 22 had aspiration pneumonia. Subsequently, 20 patients (91%) had to discontinue oral feeding entirely and 13 (59%) died, whereas, of 68 patients without pneumonia, only three patients (4%) died. Time to initial development of pneumonia was strongly correlated with survival time (Spearman R = 0.92, P<0.001), with a mean latency of 2.3 years to death. Among baseline clinical features, early fall episodes and cognitive decline were significant predictors of pneumonia (P = 0.001 and P<0.001, respectively, log rank test). Cox regression analysis demonstrated that early fall episodes (adjusted hazard ratio: 3.9, 95% confidence interval: 1.2–12.5, P = 0.03) and cognitive decline (adjusted hazard ratio: 5.2, 95% confidence interval: 1.4–19.3, P = 0.02) independently predicted pneumonia. By contrast, dysphagia was not associated with pneumonia (P = 0.2, log rank test).ConclusionInitial development of pneumonia indicates an unfavorable clinical course and predicts survival time (mean survival time 2.3 years). Patients with early falls and cognitive decline were at high risk of early development of pneumonia.

Writing in Richardson variant of progressive supranuclear palsy in comparison to progressive non-fluent aphasia

BackgroundThe overlap between progressive supranuclear palsy (PSP) and progressive non-fluent aphasia (PNFA) is being increasingly recognized. In this paper descriptive writing in patients with Richardson syndrome of progressive supranuclear palsy (PSP-RS) is compared to writing samples from patients with PNFA. MethodsTwenty-seven patients participated in the study: 17 with the clinical diagnosis of PSP-RS and 10 with PNFA. Untimed written picture description was administered during neuropsychological assessment and subsequently scored by two raters blinded to the clinical diagnosis. Lexical and syntactic content, as well as writing errors (e.g. omission and perseverative errors) were analyzed. ResultsIn patients with PSP-RS both letter and diacritic mark omission errors were very frequent. Micrographia was present in 8 cases (47%) in PSP-RS group and in one case (10%) with PNFA. Perseverative errors did not differentiate between the groups. ConclusionsAs omission errors predominate in writing of patients with PSP-RS, writing seems to be compromised mainly because of oculomotor deficits, that may alter visual feedback while writing.

MM2 subtype of sporadic Creutzfeldt-Jakob disease may underlie the clinical presentation of progressive supranuclear palsy

The classical presentation of sporadic Creutzfeldt-Jakob disease (sCJD) is rapid progressive dementia often associated with myoclonus and ataxia followed by death in less than a year from diagnosis. The few patients in the literature who presented with parkinsonism and who were suspected to have progressive supranuclear palsy (PSP) all ran a malignant course and most of them died within 3 years of diagnosis. We screened the Queen Square Brain Bank database and, among 213 patients with a clinical diagnosis of PSP, we found ten patients with 3 years or less disease duration, including one patient with CJD pathology. We report this patient and review other similar cases from the literature. Ten additional cases with similar presentation were identified in the literature. The mean disease duration was 24.2 months. The classical clinical, radiological and laboratory findings for sCJD were absent in the majority of these cases. Clinical presentation of these patients consists of: early falls, prominent dementia, early vertical supranuclear gaze palsy and symmetric akinetic syndrome. In the patients who were subtyped at post-mortem, all four represented the MM2 subtype of sCJD. A rapidly progressive course of PSP with early falls, cognitive impairments and vertical supranuclear gaze palsy should raise suspicion of underlying sCJD pathology regardless of absence of supportive findings on ancillary tests. This case and the literature support the notion that biochemical properties of the prion protein can influence the clinical presentation of sCJD.

Evidence for a role of the rare p.A152T variant in MAPT in increasing the risk for FTD-spectrum and Alzheimer's diseases

Rare mutations in the gene encoding for tau (MAPT, microtubule-associated protein tau) cause frontotemporal dementia-spectrum (FTD-s) disorders, including FTD, progressive supranuclear palsy (PSP) and corticobasal syndrome, and a common extended haplotype spanning across the MAPT locus is associated with increased risk of PSP and Parkinson's disease. We identified a rare tau variant (p.A152T) in a patient with a clinical diagnosis of PSP and assessed its frequency in multiple independent series of patients with neurodegenerative conditions and controls, in a total of 15 369 subjects. Tau p.A152T significantly increases the risk for both FTD-s (n = 2139, OR = 3.0, CI: 1.6-5.6, P = 0.0005) and Alzheimer's disease (AD) (n = 3345, OR = 2.3, CI: 1.3-4.2, P = 0.004) compared with 9047 controls. Functionally, p.A152T (i) decreases the binding of tau to microtubules and therefore promotes microtubule assembly less efficiently; and (ii) reduces the tendency to form abnormal fibers. However, there is a pronounced increase in the formation of tau oligomers. Importantly, these findings suggest that other regions of the tau protein may be crucial in regulating normal function, as the p.A152 residue is distal to the domains considered responsible for microtubule interactions or aggregation. These data provide both the first genetic evidence and functional studies supporting the role of MAPT p.A152T as a rare risk factor for both FTD-s and AD and the concept that rare variants can increase the risk for relatively common, complex neurodegenerative diseases, but since no clear significance threshold for rare genetic variation has been established, some caution is warranted until the findings are further replicated.

Instability of syllable repetition in progressive supranuclear palsy

Dysarthria is a prominent feature of progressive supranuclear palsy (PSP) and consists--amongst other features--of impaired speech fluency. Since in Parkinson's disease (PD) steadiness of syllable repetition in the course of the performance has been shown to be impaired, the aim of the present study was to investigate if measurement of syllable repetition shows similar or even more pronounced abnormalities in PSP. Thirty six patients with the clinical diagnosis of PSP (16 PSP-Richardson syndrome/PSP-RS and 20 PSP-parkinsonism/PSP-P), 60 patients with PD and 32 healthy speakers were tested. Participants had to repeat a single syllable in a self chosen isochronous pace. Percental coefficient of variance (COV) of interval length was measured for description of pace stability throughout the performance. All patients were tested according to Unified Parkinson's Disease Rating Scale (UPDRS III). Patients with PSP were additionally scored according to PSP rating scale (PSPRS). In the PSP group, COV was significantly worse not only when compared with healthy speakers but also when compared with PD patients of similar disease duration and similar global motor impairment. COV showed only a trend to higher values in the subgroup with PSP-RS as compared to PSP-P. In the PSP-P, but not in the PSP-RS subgroup, there was a positive correlation between COV and PSPRS/UPDRS III. PSP patients feature more pronounced difficulties in the steady syllable repetition than patients with PD and healthy controls as a hint for a more profound dysfunction of basal motor speech performance in PSP than in PD.

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.

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.

Steele-Richardson-Olszewski-Syndrom

Basal ganglia diseases with an akinetic-rigid symptom manifest like a Parkinson disease or an atypical Parkinson syndrome. Their symptoms are similar and therefore a diagnosis often is only possible after long-standing care of the patient. In the class of the atypical Parkinson syndromes is the progressive supranuclear palsy (PSP), which is also known as Steele-Richardson-Olszewski syndrome. A seventy-year-old patient who reported unaccountable sudden drops and disturbances of balance as well as diplopia in near vision was examined and a retrospective analysis of the case history was carried out. Only long-standing observation of the patient rendered the suspected diagnosis of a progressive supranuclear palsy (PSP) possible. Only after determination of the clinic picture of a vertical palsy to the up and the down direction and a bad optokinetic nystagmus with an existing vertical vestibular reflex could the clinical diagnosis of PSP be confirmed. In cases with the combination of a vertical palsy, an akinetic-rigid Parkinson syndrome, pyramidal tract signs and subcortical dementia, the diagnosis of a suspected progressive supranuclear palsy should be made. L-Dopa medication has very little or no influence on PSP. At present, however, a certain diagnosis is only possible post-mortem, in spite of helpful clinical diagnostics.

Cerebrospinal fluid analysis for Whipple's disease in patients with progressive supranuclear palsy.

The clinical picture of neurological involvement in Whipple's disease (WD) may resemble progressive supranuclear palsy (PSP). We looked for WD pathogen DNA in the cerebrospinal fluid of 9 patients with a clinical diagnosis of PSP. The analysis was negative for all samples, showing that WD is not commonly involved in the aetiopathogenesis of PSP.

Progressive supranuclear palsy: clinical features, pathophysiology and management.

Progressive supranuclear palsy (PSP) is a degenerative condition of unknown aetiology that produces an akinetic-rigid form of parkinsonism characterised by early falls and abnormalities of extraocular movements. Mean age of onset is approximately 63 years, and mean survival from symptom onset is 9 years. Men are much more frequently affected than women. The classic clinical finding is supranuclear ophthalmoplegia, which may not present until late in the illness, if at all. The clinical diagnosis of PSP can be difficult to make, as the sites of pathology are heterogeneous. Structural and functional neuroimaging studies, although not specific for PSP, may be of some assistance in making the diagnosis. The definitive diagnosis of PSP requires the presence of both clinical and neuropathological evidence. Multiple anatomical sites are affected in PSP. The most consistently involved are the subthalamic nucleus, globus pallidus interna and externa, pontine nuclei, periaqueductal grey matter and the substantia nigra. The location of the pathology accounts for the clinical features. The histological hallmark of PSP is the presence of globose neurofibrillary tangles in the affected subcortical nuclei. Neurofibrillary tangles are composed of abnormally phosphorylated tau, a microtubule-associated protein that is involved in maintenance of the cytoskeleton. Abnormalities near or in the gene coding for tau are implicated in the pathogenesis of PSP. The multiple neurotransmitter abnormalities, including those affecting dopamine, acetylcholine, gamma-aminobutyric acid and norepinephrine (noradrenaline) systems and pathways, as well as both pre- and post-synaptic pathology, make pharmacological therapy of PSP a challenge. Although an individual patient may respond to a drug, in general patients with PSP have a minimal response and a short duration of sustained benefit.