Gene/Protein Disease Symptom Drug Enzyme Compound
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Query: UMLS:C0013362 (dysarthria)
 3,768 document(s) hit in 31,850,051 MEDLINE articles (0.00 seconds)

Progressive supranuclear palsy (PSP) is an atypical Parkinsonian disorder associated with progressive axial rigidity, vertical gaze palsy, dysarthria and dysphagia. Neuropathologically, the subthalamic nucleus and brainstem, especially the midbrain tectum and the superior cerebellar peduncle, show atrophy. The substantia nigra shows loss of pigment corresponding to nigrostriatal dopaminergic degeneration. Microscopic findings include neuronal loss, gliosis and neurofibrillary tangles in basal ganglia, diencephalon and brainstem. Characteristic tau pathology is also found in glia. The major genetic risk factor for sporadic PSP is a common variant in the gene encoding microtubule-associated protein tau (MAPT) and recent studies have suggested that this may result in the altered expression of specific tau protein isoforms. Imaging studies suggest that there may be sensitive and specific means to differentiate PSP from other parkinsonian disorders, but identification of a diagnostic biomarker is still elusive.
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PMID:Progressive supranuclear palsy: pathology and genetics. 1749 41

We present 3 sporadic cases of a subacute to chronic, progressive motor (i.e. weakness, ataxia, spasticity, dysarthria, and dysphagia) and cognitive disorder in adults of both sexes, without proven immunocompromise or malignancy. Neuroimaging studies revealed tiny calcifications with atrophy of the cerebrum, pons, and midbrain in 1 patient, cerebral atrophy in another, and cerebral atrophy and periventricular white matter hyperintensities in the third. Clinical diagnoses included cortico-pontine-cerebellar degeneration, mixed neurodegenerative disorder, progressive supranuclear palsy, diffuse Lewy body disease, and Lyme disease. One atrophic brain revealed widely disseminated, millimeter-sized gray lesions in cerebral white matter and obscured anatomic markings of the basis pontis. The most conspicuous microscopic feature in all was capillaries with focally piled up endothelial nuclei, some of which appeared to be multinucleated, or enlarged, hyperchromatic crescentic single nuclei. Although seen mostly without associated damage, they were also noted with white matter lesions displaying vacuolation, demyelination, spheroids, necrosis, vascular fibrosis, and mineralization; these were most severe in the basis pontis. Immunostains and probes to herpes simplex virus-I, -II, and -8; adenovirus, cytomegalovirus, varicella-zoster, Epstein-Barr virus, measles, JC virus, and herpes hominis virus-6 were negative. Electron microscopy revealed no virions in endothelial cells with multilobed or multiple nuclei and duplicated basal laminae. However, mycoplasma-like bodies, mostly 400 to 600 nm in size, were found in endothelial cell cytoplasm and capillary lumina. Platelets adhered to affected endothelial cells. Polymerase chain reaction and immunohistochemistry of fixed samples for Mycoplasma fermentans were negative; other species of Mycoplasma remain viable pathogenic candidates.
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PMID:A novel cerebral microangiopathy with endothelial cell atypia and multifocal white matter lesions: a direct mycoplasmal infection? 2300 Dec 18

Progressive supranuclear palsy (PSP) typically presents with a gradual onset and progressive course of symmetric levodopa-unresponsive parkinsonism characterized by postural instability with falls, supranuclear vertical gaze palsy, dysarthria, dysphagia, and cognitive and behavioral disturbances. Though the clinical course is variable, the typical presentation is usually associated with mortality at 5-9 years after symptom onset. The pathological hallmark of PSP is widespread neuronal cell loss with deposition of aggregated hyperphosphorylated tau, particularly within the midbrain. Etiology remains elusive, but a variable combination of genetic, environmental, oxidative stress, and inflammatory factors may all contribute. Genetic advances have confirmed the H1 tau haplotype on chromosome 17q21.31 to be associated with PSP, while the H2 haplotype seems protective. With greater knowledge of the molecular and genetic aspects of PSP, we can expect future diagnostic and therapeutic challenges to be more effectively met.
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PMID:Unraveling progressive supranuclear palsy: from the bedside back to the bench. 1826 62

A neurological syndrome characterized by levodopa unresponsive bradykinesia, retropulsion with falls backwards, dysarthria, gait disturbance, dystonia, and emotional lability was identified in 13 male opiate addicts following the prolonged intravenous use of ephedrone (methcathinone), a central nervous stimulant prepared from pseudoephedrine, potassium permanganate, and vinegar. The natural history, response to treatment, and clinical features has been studied, and MR and dopamine transporter SPECT brain imaging were carried out. Pubic hair was sampled for manganese. The clinical and radiological picture closely resembled previous reports of chronic manganese poisoning and increased mean manganese level in pubic hair observed for at least 1 year after cessation of ephedrone. Odor identification was intact. Cognitive assessment showed a mild executive dysfunction and a mild depression. DaTSCANs were all normal. The neurological syndrome bears some similarities to PSP but differs from Parkinson's disease. Delayed neurological progression despite discontinuation of ephedrone occurred in one-third of cases. Ephedrone poisoning should be considered as a possible cause of secondary Parkinsonism in young adults, particularly from Eastern Europe.
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PMID:Parkinsonism and dystonia caused by the illicit use of ephedrone--a longitudinal study. 1878 45

Basophilic Inclusion Body Disease (BIBD) is a tau-negative form of frontotemporal lobar degeneration (FTLD), characterized by neuronal cytoplasmic inclusions (NCI) that are visible on hematoxylin and eosin stain (HE), contain RNA, and are inconsistently ubiquitin-immunoreactive (ir). The normal nuclear expression of TDP-43 is not altered. Here we investigate whether the distribution of the structurally and functionally related protein fused in sarcoma (FUS) is altered in BIBD. Mutations in the FUS gene have recently been identified as a cause of familial amyotrophic lateral sclerosis (ALS). In addition to these familial ALS cases, FUS protein has recently been demonstrated in NCI in a subset of FTLD with ubiquitinated inclusions (atypical FTLD-U) and in neuronal intermediate filament inclusion disease (NIFID). We examined seven BIBD brains of patients with average age at onset 46 (range 29-57) and average duration of disease 8 years (range 5-12). Three cases presented with the behavioural variant of fronto-temporal dementia (FTD-bv) and one with FTD-bv combined with severe dysarthria. All four developed motor neuron disease/ALS syndrome (MND/ALS) several years later. In the other three cases, presentation was predominantly with motor symptoms, construed as MND/ALS in two, and progressive supranuclear palsy (PSP) in one. Severity of cortical degeneration varied, but all cases shared severe nigrostriatal atrophy and lower motor neuron pathology. In spared areas of cortex, FUS antibodies showed intense labelling of neuronal nuclei and weak positivity of cytoplasm, whereas, in affected areas, intense labelling of NCI was accompanied by reduction or disappearance of the normal IR pattern. The number of FUS-ir NCI was much greater than the number detected by HE or with ubiquitin or P62 immunohistochemistry. FUS-ir glial cytoplasmic inclusions (GCI) were abundant in the grey and white matter in all cases, whereas neuronal intranuclear inclusions were rare and only seen in 2/7 cases. Thus, BIBD shares with atypical FTLD-U and NIFID the presence of FUS-ir NCI and GCI, and together comprise a new biochemical category of neurodegenerative disease (FUS proteinopathies). The consistent involvement of motorneurons in BIBD indicates that the association of FTLD and MND/ALS can occur on a FUS or TDP-43 pathological substrate.
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PMID:FUS pathology in basophilic inclusion body disease. 1984 30

Progressive supranuclear palsy (PSP) is a neurodegenerative disease characterized by vertical supranuclear palsy and parkinsonian symptoms. The neuropsychiatric symptoms of PSP include anhedonia, depressed mood and cognitive impairment. Patients with PSP have an increased risk for developing depressive disorders within the next year. However, it is rare to find that major depressive disorder was the antecedent diagnosis of a patient who was later diagnosed with PSP. We present here a patient who suffered from PSP with repetitive falls, a masked face and dysarthria after developing a major depressive disorder.
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PMID:Major depressive disorder preceding the onset of progressive supranuclear palsy. 2004 84

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.
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PMID:Endoscopic characteristics and levodopa responsiveness of swallowing function in progressive supranuclear palsy. 2062 30

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.
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PMID:[An autopsied case of progressive supranuclear palsy, initially diagnosed as spinocerebellar degeneration with severe olivopontocerebellar involvement]. 2201 67

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.
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PMID:Instability of syllable repetition in progressive supranuclear palsy. 2206 10

We report an autopsy case of progressive supranuclear palsy (PSP) that clinically showed only slowly progressive and symmetric upper motor neuron syndrome over a disease course of 12 years. A female patient initially exhibited dysarthria at the age of 65, followed by gait disturbance and dysphagia. Neurological examination at age 67 disclosed pseudobulbar palsy, spastic gait, hyperreflexia, and presence of bilateral Hoffmann and Babinski signs. However, muscle atrophy, weakness, evidence of denervation on electromyography, vertical gaze palsy, parkinsonism, gait freezing, aphasia, speech apraxia, or dementia was not noted throughout the course. She was clinically diagnosed as having motor neuron disease consistent with so-called primary lateral sclerosis. Pathological examination disclosed histopathological features of PSP, including argyrophilic and tau-positive tufted astrocytes, neurofibrillary tangles, coiled bodies, and thread-like processes in the motor cortex and superior frontal gyrus, and to a lesser degree, in the basal ganglia and brain stem nuclei. In addition, severe fibrillary gliosis was noted in the precentral gyrus and corticospinal tract, being consistent with upper motor neuron syndrome observed in this case. No TAR-DNA binding protein 43-positive lesion, FUS pathology, Bunina body, or Lewy body-like hyaline inclusion was noted in the motor cortex or lower motor neurons. These findings suggest that when tau pathology is prominent in the motor cortex but is minimal in the basal ganglia and brain stem nuclei, a PSP case can lack all classic clinical features of PSP and show only slowly progressive upper motor syndrome, consistent with clinical picture of primary lateral sclerosis.
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PMID:Progressive supranuclear palsy presenting as primary lateral sclerosis but lacking parkinsonism, gaze palsy, aphasia, or dementia. 2357 Sep 81


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