Progressive Supranuclear Gaze Palsy with Predominant Cerebellar Ataxia: A Case Series with Videos.
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SUBMITTER: Xu Z
PROVIDER: S-EPMC5435833 | biostudies-literature | 2017 May
REPOSITORIES: biostudies-literature
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Progressive Supranuclear Gaze Palsy with Predominant Cerebellar Ataxia: A Case Series with Videos.
Xu Zheyu Z Lim Tchoyoson C C TCC Au Wing Lok WL Tan Louis C S LCS
Journal of movement disorders 20170418 2
Progressive supranuclear palsy (PSP) with predominant cerebellar ataxia (PSP-C) is a rare phenotype of PSP. The clinical and radiological features of this disorder remain poorly characterized. Through a retrospective case series, we aim to characterize the clinical and radiological features of PSP-C. Four patients with PSP-C were identified: patients who presented with prominent cerebellar dysfunction that disappeared with the progression of the disease. Supranuclear gaze palsy occurred at a mea ...[more]
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Project description:We report a 63-year-old female patient with progressive supranuclear palsy (PSP). She presented predominant postural instability and "saccadic ping-pong gaze" (SPPG). She had unprovoked falls recurrently within a year from the onset of gait disturbance. She tended to fall backward with eye closure but had no freezing of gait on examination. She showed no signs of nuchal dystonia, limb tremor, rigidity, spasticity, or ataxia. The dopaminergic response was negative. On the initial examination, her vertical eye movements were normal, but frequent macro square wave jerks and SPPG were observed. SPPG consisted of short-cycle, horizontal conjugate irregular pendular oscillations of the eye position from the midpoint with superimposed small saccades. SPPG was observed usually in the dark, not in the daylight, and with eye closure by using electrooculogram and infrared charge-coupled device imaging. One and a half years after the first examination, she was diagnosed as probable PSP with vertical supranuclear gaze palsy. SPPG was first described in patients who are unconscious by Johkura in 1998 as a "saccadic" variant of "ping-pong gaze (PPG)." PPG, short-cycle periodic alternating gaze, has been described in comatose patients since 1967. On the other hand, abnormal eye movement, which looks the same as SPPG in coma, has been described in conscious patients with PSP or spinocerebellar degeneration (SCD) in Japanese literature since 1975. However, it has been called "transient alternating saccades (TAS)." Nowadays, we believe it is more appropriate to call this abnormal eye movement "SPPG" instead of TAS. Here, we propose that PSP, a neuro-degenerative disease, should be added as one of the etiologies of SPPG. We discuss the differences between PPG/SPPG in coma and SPPG in PSP and the possible pathophysiological mechanism of SPPG in relation to cerebellar oculomotor dysfunctions.
| S-EPMC10014735 | biostudies-literature
Project description:BackgroundCerebellar ataxia is an exclusion criterion for the clinical diagnosis of progressive supranuclear palsy, but a variant with predominant cerebellar ataxia has been reported. The aims of this study were to estimate the frequency of progressive supranuclear palsy with predominant cerebellar ataxia in an autopsy series from the United States and to compare clinical, pathologic, and genetic differences between progressive supranuclear palsy with and without predominant cerebellar ataxia.MethodWe selected 100 consecutive patients with pathologically confirmed progressive supranuclear palsy who had been evaluated at the Mayo Clinic (referred to as the Mayo Clinic patient series) from our brain bank database (N = 1085). We next enriched in cases likely to have cerebellar ataxia by searching the remaining 985 cases for (1) an antemortem diagnosis of multiple system atrophy or (2) neuropathologic evidence of prominent degeneration of the cerebellum or cerebellar afferent nuclei. Subsequently, clinical, pathologic, and genetic features were compared between the two groups.ResultsOne patient in the Mayo Clinic patient series (1%) met criteria for progressive supranuclear palsy with predominant cerebellar ataxia and had both cerebellar and mild midbrain atrophy on MRI. Four patients were identified with the targeted search. Four of the five patients were clinically misdiagnosed as multiple system atrophy. The severity of tau-related pathology and cerebellar degeneration were not different between the two groups. No differences were detected in tau genotypes.ConclusionAlthough our data cannot provide definitive information about how to make an accurate clinical diagnosis, they should serve to raise awareness of progressive supranuclear palsy with predominant cerebellar ataxia in the differential diagnosis of multiple system atrophy. © 2016 Movement Disorder Society.
| S-EPMC4861661 | biostudies-literature
Project description:Progressive supranuclear palsy is a sporadic neurodegenerative 4-repeat tauopathy associated with significant morbidity. Heterogeneity of symptom expression among this group is increasingly recognized, reflecting variable tau spread and neurodegeneration. Clinical manifestations consist of debilitating and rapidly progressive motor, oculomotor, speech, cognitive and affective impairments. Core pathological changes are noted with a predominance in the midbrain and basal ganglia; however, spread to the more caudal brainstem and cerebellar regions is reported at various stages. Accordingly, whilst midbrain atrophy is the best recognized supportive imaging finding, quantitative neuroimaging studies using MRI and PET approaches have revealed a wider profile of brain abnormalities in cohorts of individuals with progressive supranuclear palsy. This expanded neurobiological scope of disease may account for individual heterogeneity and may highlight additional biological markers that are relevant to diagnosing and tracking the illness. Additionally, there is increasing understanding of the diverse cognitive, affective and speech functions of the cerebellum, which may be implicated in progressive supranuclear palsy beyond current recognition. In this review, we undertake a systematic literature search and summary of in vivo structural and functional neuroimaging findings in the brainstem and cerebellum in progressive supranuclear palsy to date. Novel and multimodal imaging techniques have emerged over recent years, which reveal several infratentorial alterations beyond midbrain atrophy in progressive supranuclear palsy. Most saliently, there is evidence for volume loss and microstructural damage in the pons, middle cerebellar peduncles and cerebellar cortex and deep nuclei, reported alongside recognized midbrain and superior cerebellar peduncle changes. Whilst the literature supporting the presence of these features is not unanimous, the evidence base is compelling, including correlations with disease progression, severity or variant differences. A smaller number of studies report on abnormalities in MRI measures of iron deposition, neuromelanin, viscoelasticity and the glymphatic system involving the infratentorial regions. Molecular imaging studies have also shown increased uptake of tau tracer in the midbrain and cerebellar dentate nucleus, although concern remains regarding possible off-target binding. Imaging of other molecular targets has been sparse, but reports of neurotransmitter, inflammatory and synaptic density alterations in cerebellar and brainstem regions are available. Taken together, there is an established evidence base of in vivo imaging alterations in the brainstem and cerebellum which highlights that midbrain atrophy is often accompanied by other infratentorial alterations in people with progressive supranuclear palsy. Further research examining the contribution of these features to clinical morbidity and inter-individual variability in symptom expression is warranted.
| S-EPMC11829206 | biostudies-literature
Project description:Mounting evidence suggests an association between cerebellar atrophy and cognitive impairment in the main frontotemporal dementia syndromes. In contrast, whether cerebellar atrophy is present in the motor syndromes associated with frontotemporal lobar degeneration (corticobasal syndrome and progressive supranuclear palsy) and the extent of its contribution to their cognitive profile remain poorly understood. The current study aimed to comprehensively chart profiles of cognitive impairment in relation to cerebellar atrophy in 49 dementia patients (corticobasal syndrome = 33; progressive supranuclear palsy = 16) compared to 33 age-, sex- and education-matched healthy controls. Relative to controls, corticobasal syndrome and progressive supranuclear palsy patients demonstrated characteristic cognitive impairment, spanning the majority of cognitive domains including attention and processing speed, language, working memory, and executive function with relative preservation of verbal and nonverbal memory. Voxel-based morphometry analysis revealed largely overlapping patterns of cerebellar atrophy in corticobasal syndrome and progressive supranuclear palsy relative to controls, primarily involving bilateral Crus II extending into adjacent lobules VIIb and VIIIa. After controlling for overall cerebral atrophy and disease duration, exploratory voxel-wise general linear model analysis revealed distinct cerebellar subregions differentially implicated across cognitive domains in each patient group. In corticobasal syndrome, reduction in grey matter intensity in the left Crus I was significantly correlated with executive dysfunction. In progressive supranuclear palsy, integrity of the vermis and adjacent right lobules I-IV was significantly associated with language performance. These results are consistent with the well-established role of Crus I in executive functions and provide further supporting evidence for vermal involvement in cognitive processing. The current study presents the first detailed exploration of the role of cerebellar atrophy in cognitive deficits in corticobasal syndrome and progressive supranuclear palsy, offering insights into the cerebellum's contribution to cognitive processing even in neurodegenerative syndromes characterized by motor impairment.
| S-EPMC7753056 | biostudies-literature
Project description:The differential diagnosis of MSA-P and PSP-P remains a difficult issue in clinical practice due to their overlapping clinical manifestation and the lack of tools enabling a definite diagnosis ante-mortem. This paper describes the usefulness of SPECT HMPAO in MSA-P and PSP-P differentiation through the analysis of cerebellar perfusion of small ROIs. Thirty-one patients were included in the study-20 with MSA-P and 11 with PSP-P; the analysis performed indicated that the most significant difference in perfusion was observed in the anterior quadrangular lobule (H IV and V) on the left side (p < 0.0026). High differences in the median perfusion between the groups were also observed in a few other regions, with p < 0.05, but higher than premised p = 0.0026 (the Bonferroni correction was used in the statistical analysis). The assessment of the perfusion may be interpreted as a promising method of additional examination of atypical parkinsonisms with overlapping clinical manifestation, as in the case of PSP-P and MSA-P. The results obtained suggest that the interpretation of the differences in perfusion of the cerebellum should be made by evaluating the subregions of the cerebellum rather than the hemispheres. Further research is required.
| S-EPMC9776891 | biostudies-literature
Project description:The cerebrospinal fluid miRNAs expression was markedly altered in the patients with progressive supranuclear palsy and controls.
2021-12-05 | GSE186921 | GEO
Project description:IntroductionThere is growing interest in using patient-reported outcomes as end points in clinical trials, such as the progressive supranuclear palsy quality of life (PSP-QoL) scale. However, this tool has not been widely validated and its correlation with validated motor scales has not been explored. To evaluate the potential utility of using PSP-QoL as an outcome, it is important to examine its relationship with a standard scale used to evaluate neurologic parameters, such as the PSP Rating Scale.MethodsPSP-QoL and PSP Rating Scale scores were gathered from 60 clinically diagnosed PSP patients, including patients with Richardson syndrome PSP (PSP-RS, n = 43) and those with non-RS PSP variants (n = 17). Linear regression analysis adjusted for age, sex, and disease duration was used to evaluate the cross-sectional relationship between the total and subscale scores of the 2 instruments.ResultsAmong 60 PSP patients, there was a significant correlation between total PSP-QoL and PSP Rating Scale scores. The physical and mentation subscales of each instrument also demonstrated significant correlations. Comparisons among PSP subtypes indicated that worsening PSP-QoL Total and Physical subscale scores correlated with worsening PSP Rating Scale gait subscale scores more strongly for the non-RS PSP variants than for PSP-RS.DiscussionThere is a significant association between the total scores and many of the subscale scores of the PSP-QoL and the PSP Rating Scale. Additionally, the relationship between these measures may differ for PSP-RS and non-RS variants. These findings suggest that the PSP-QoL may be useful in clinical trials as a patient-reported outcome measure. Large prospective multicenter studies utilizing the PSP-QoL are necessary to examine its relationship to disease evolution and changes in the PSP Rating Scale.
| S-EPMC8119324 | biostudies-literature
Project description:Background and purposeProgressive supranuclear palsy (PSP) encompasses a broader range of disease courses than previously appreciated. The most frequent clinical presentations of PSP are Richardson syndrome (RS) and PSP with a predominant Parkinsonism phenotype (PSP-P). Time to reach gait dependence and cognitive impairment have been proposed as prognostic disease milestones. Genetic polymorphisms in TRIM11 and SLC2A13 genes have been associated with longer disease duration (DD).MethodsMethods used include retrospective chart review, genetic single nucleotide polymorphism analyses (in three cases), and neuropathology.ResultsWe identified four cases with long (>10-15 years) or very long (>15 years) DD. Stage 1 PSP tau pathology was present in two cases (one PSP-P and one undifferentiated phenotype), whereas pallidonigroluysian atrophy (PSP-RS) and Stage 4/6 (PSP-P) PSP pathology were found in the other two cases. Three cases were homozygous for the rs564309-C allele of the TRIM11 gene and the H1 MAPT haplotype. Two were heterozygous for rs2242367 (G/A) in SLC2A13, whereas the third was homozygous for the G-allele.ConclusionsWe propose a protracted course subtype of PSP (PC-PSP) based on clinical or neuropathological criteria in two cases with anatomically restricted PSP pathology, and very long DD and slower clinical progression in the other two cases. The presence of the rs564309-C allele may influence the protracted disease course. Crystallizing the concept of PC-PSP is important to further understand the pathobiology of tauopathies in line with current hypotheses of protein misfolding, seeding activity, and propagation.
| S-EPMC10276574 | biostudies-literature
Project description:IntroductionTremor is thought to be a rare feature of progressive supranuclear palsy (PSP).MethodsWe retrospectively reviewed the database of the CurePSP brain bank at Mayo Clinic Florida to retrieve all available clinical information for PSP patients. All patients underwent a standard neuropathological assessment and an immunohistochemical evaluation for tau and α-synuclein. DNA was genotyped for the MAPT H1/H2 haplotype.ResultsOf the 375 PSP patients identified, 344 had a documented presence or absence of tremor, which included 146 (42%) with tremor, including 29 (20%) with postural/action tremors, 16 (11%) with resting tremor, 7 (5%) with intention tremor, 20 (14%) with a combination of different types of tremor, and 74 (51%) patients who had tremor at some point during their illness, but details were unavailable. The tremor severity of 96% of the patients (54/55) who had this data was minimal to mild. The probability of observing a tremor during a neurological examination during the patient's illness was estimated to be ∼22%. PSP patients with postural/action tremors and PSP patients with resting tremor responded to carbidopa-levodopa therapy more frequently than PSP patients without tremor, although the therapy response was always transient. There were no significant differences in pathological findings between the tremor groups.ConclusionsTremor is an inconspicuous feature of PSP; however, 42% (146/344) of the PSP patients in our study presented some form of tremor. Because there is no curative therapy for PSP, carbidopa/levodopa therapy should be tried for patients with postural, action, and resting tremor.
| S-EPMC4887294 | biostudies-literature
Project description:Progressive supranuclear palsy (PSP) is a neurodegenerative syndrome that is clinically characterized by progressive postural instability, supranuclear gaze palsy, parkinsonism and cognitive decline. Pathologically, diagnosis of PSP is based on characteristic features, such as neurofibrillary tangles, neutrophil threads, tau-positive astrocytes and their processes in basal ganglia and brainstem, and the accumulation of 4 repeat tau protein. PSP is generally recognized as a sporadic disorder; however, understanding of genetic background of PSP has been expanding rapidly. Here we review relevant publications to outline the genetics of PSP. Although only small number of familial PSP cases have been reported, the recognition of familial PSP has been increasing. In some familial cases of clinically probable PSP, PSP pathologies were confirmed based on NINDS neuropathological diagnostic criteria. Several mutations in MAPT, the gene that causes a form of familial frontotemporal lobar degeneration with tauopathy, have been identified in both sporadic and familial PSP cases. The H1 haplotype of MAPT is a risk haplotype for PSP, and within H1, a sub-haplotype (H1c) is associated with PSP. A recent genome-wide association study on autopsyproven PSP revealed additional PSP risk alleles in STX6 and EIF2AK3. Several heredodegenerative parkinsonian disorders are referred to as PSP-look-alikes because their clinical phenotype, but not their pathology, mimics PSP. Due to the fast development of genomics and bioinformatics, more genetic factors related to PSP are expected to be discovered. Undoubtedly, these studies will provide a better understanding of the pathogenesis of PSP and clues for developing therapeutic strategies.
| S-EPMC4572662 | biostudies-literature